Conference Coverage

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Phase 3 data support rilzabrutinib as a potential first-in-class oral Bruton tyrosine kinase (BTK) inhibitor for patients with previously treated immune thrombocytopenia (ITP). 

In the LUNA 3 trial, treatment with rilzabrutinib (Sanofi) led to rapid and durable platelet responses, reduced bleeding and need for rescue therapy, and improved health-related quality of life in patients with persistent or chronic immune thrombocytopenia. 

Notably, rilzabrutinib also “significantly improved fatigue, even among patients who did not have a significant platelet count rise,” said David J. Kuter, MD, DPhil, director of clinical hematology, Massachusetts General Hospital, Boston, who reported the findings during a press briefing at the American Society of Hematology (ASH) 2024 Annual Meeting.

Briefing moderator Charles Abrams, MD, University of Pennsylvania, Philadelphia, noted that LUNA 3 enrolled a “remarkably tough group of patients, really the hardest of the hard” and showed that rilzabrutinib was “well-tolerated and caused an increase in platelet counts.”

The study, Abrams added, demonstrates “significant progress” in treatment of a disease that has historically been viewed as “benign,” which is “good for our patients.”

Immune thrombocytopenia is a relatively rare autoimmune disease that affects 10 to 23 patients per 100,000 in the United States. For those with the condition, the body’s immune system attacks platelets, causing platelet counts to drop below 100,000/μL of blood. The disease leads to increased bleeding risk and thrombosis, impaired clotting and health-related quality of life, as well as greater fatigue. 

“People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies,” Kuter noted in a Sanofi news release. 

Rilzabrutinib, which received fast-track designation in November 2020 from the US Food and Drug Administration to treat immune thrombocytopenia, is currently under regulatory review and has a target action date of August 29, 2025. 

In the LUNA 3 study, adults with persistent or chronic immune thrombocytopenia and severely low platelet counts (median, 15,000/μL) received oral rilzabrutinib 400 mg twice a day (133 patients) or placebo (69 patients) for up to 24 weeks during a blinded treatment period, followed by a 28-week open-label period.

Platelet response — defined as counts at or above 50,000/μL or counts between 30,000/μL and 50,000/μL but doubled from baseline — was achieved in nearly two thirds of patients taking rilzabrutinib compared with almost one third of patients taking placebo at week 13. 

The primary endpoint was durable platelet response, defined as the proportion of patients able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded period, without the need for rescue therapy. 

No patient taking placebo met this endpoint, compared with 23% of patients taking rilzabrutinib (P < .0001).

For the combined double-blind and open-label periods, a durable response was achieved in 29% of the 133 patients randomized to rilzabrutinib and 25% of the 193 patients receiving the drug in the open-label period at the data cutoff. 

Rilzabrutinib also led to significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change from baseline at week 25 of –0.04 with rilzabrutinib versus 0.05 with placebo (P = .0006).

Patients on rilzabrutinib were three times more likely to achieve a platelet response than their peers on placebo (hazard ratio, 3.1; P < .0001), with a median time to first platelet response of 36 days (vs median not achieved by patients on placebo). Among patients randomized to rilzabrutinib who achieved a response, the median time to response was 15 days.

Compared with placebo, rilzabrutinib significantly reduced the need for rescue therapy by 52% (P = .0007).

Rilzabrutinib was also associated with significant and sustained improvement in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire [ITP-PAQ] Item 10 score).

“To our surprise, those patients who got active therapy but did not have a durable response still had an improvement in their fatigue levels and that suggests rilzabrutinib may affect fatigue or have anti-inflammatory properties since BTK inhibition has many different elements to it,” Kuter said during the briefing. 

The most common treatment-related adverse events with rilzabrutinib versus placebo were mild to moderate (grade 1/2) diarrhea (23% vs 4%), nausea (17% vs 6%), headache (8% vs 1%), and abdominal pain (6% vs 1%). Rates of grade 2 or higher gastrointestinal adverse events were comparable between groups: 6% with rilzabrutinib versus 4% with placebo. In the rilzabrutinib group, one patient who had numerous risk factors had a treatment-related grade 3 peripheral embolism and one patient died due to pneumonia unrelated to treatment.

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” Kuter said in the Sanofi news release. 

The LUNA 3 study was funded by Sanofi. Kuter has disclosed various relationships with Sanofi and other pharmaceutical companies.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

A version of this article first appeared on Medscape.com.

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

A version of this article first appeared on Medscape.com.

SAN DIEGO — Single-agent epcoritamab demonstrated deep and durable responses in chimeric antigen receptor T (CAR T)–naïve patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) in a subgroup analysis of the pivotal phase 2 Epcore NHL-1 trial.

These findings show that epcoritamab — a bispecific antibody therapy available off the shelf and shown in the overall R/R LBCL population in Epcore NHL-1 to be effective following CAR T–cell therapy — can also be administered safely and effectively before CAR T in patients with R/R LBCL.

This is of particular note for patients who may be ineligible for CAR T or whose access to CAR T is limited, first author Yasmin H. Karimi, MD, said in an interview during a poster presentation at the annual American Society of Hematology (ASH) conference. 

With over 3 years of follow-up, epcoritamab monotherapy was associated with an overall response rate and complete response rate of 61% and 45%, respectively, in 96 CAR T-naive patients, and side effects were manageable, said Karimi, of the University of Michigan, Ann Arbor, Michigan.

In Epcore NHL-1, epcoritamab — a CD3xCD20 T-cell-engaging bispecific antibody — led to deep and durable responses with manageable toxicity in the patients with R/R LBCL including both CAR T–treated and CAR T–naive patients. The agent was subsequently approved for the treatment of adults with different types of R/R LBCL and follicular lymphoma after at least two prior lines of therapy. Among those who had received CAR T–cell therapy, the ORR/CR rates were 54% and 34%, according to results reported at ASH 2022.

Patients included in the trial were adults with R/R CD20 LBCL, including diffuse LBCL, high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and grade 3B follicular lymphoma with at least two prior lines of systemic antilymphoma therapy. They were treated with two step-up doses of epcoritamab followed by 48-mg full doses in 28-day cycles, including weekly treatment for cycles 1-3, biweekly treatment for cycles 4-9, and treatment every 4 weeks for cycle 10 and any subsequent cycles, until disease progression or unacceptable toxicity.

In the current subgroup analysis of 96 CAR T–naive patients, median duration of response was 18.4 months, median duration of complete response was 28.6 months, and an estimated 46% of patients remained in complete response at 36 months, Karimi said.

Median progression-free survival duration was 4.3 months overall and 33.3 months among complete responders. Median overall survival was 15.4 months and was not reached in complete responders.

At 3 years, an estimated 40% of patients overall and 83% of complete responders had not initiated any other antilymphoma therapy, and of the 35 who received subsequent antilymphoma therapy, 10 (29%) received CAR T. Six of the 10 were alive at data cutoff, and 33 of 74 patients evaluable for minimal residual disease (MRD) were MRD-negative.

The most common treatment-emergent adverse events were cytokine release syndrome (CRS) in 60% of patients, diarrhea in 24%, pyrexia in 23%, fatigue in 22%, neutropenia in 22%, and injection-site reaction in 21%. 

Fatal reactions occurred in 18 patients. Of these, nine were related to COVID-19 infection. CRS events were mostly of grade 1 or 2; 4% were of grade 3. CRS occurred most often following cycle 1 and resolved in all but two patients. ICANS occurred in seven patients, clinical tumor lysis syndrome occurred in two patients, and immunoglobulin G levels decreased by a median of about 20% after the story of treatment and remained stable over time, Karimi noted.

“These findings show that epcoritamab can be administered safely and effectively in CAR T–naive or CAR T–exposed patients with R/R LBCL,” she said.

Karimi reported relationships with AstraZeneca, Lily/Loxo, Merck, AbbVie, ADC Therapeutics, Xencor, and Roche/Genentech. 

A version of this article first appeared on Medscape.com.

WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.

“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”

Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.

“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.” 

It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.

“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.

 

Targeting Factors That Clinicians Can Potentially Influence

In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.

These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.

The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.

The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.

The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.

As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.

Providing access to at-risk patients included several components:

• Creating a population management team
• Defining a target population to engage with for earlier follow-up
• Using a monthly batch outreach to defined patients
• Having a coordinator or social worker reach out to those who don’t make appointments
• Using a new JIA/high disease activity video follow-up program.

Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.

Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.

One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.

 

Results of the Quality Improvement Project

As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.

They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.

From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.

In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.

One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.

Abel and Harry had no disclosures. No external funding was noted.

A version of this article appeared on Medscape.com.

WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.

“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”

Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.

“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.” 

It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.

“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.

 

Targeting Factors That Clinicians Can Potentially Influence

In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.

These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.

The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.

The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.

The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.

As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.

Providing access to at-risk patients included several components:

• Creating a population management team
• Defining a target population to engage with for earlier follow-up
• Using a monthly batch outreach to defined patients
• Having a coordinator or social worker reach out to those who don’t make appointments
• Using a new JIA/high disease activity video follow-up program.

Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.

Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.

One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.

 

Results of the Quality Improvement Project

As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.

They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.

From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.

In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.

One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.

Abel and Harry had no disclosures. No external funding was noted.

A version of this article appeared on Medscape.com.

WASHINGTON — A quality improvement project aimed at reducing racial disparities in juvenile idiopathic arthritis (JIA) led to a modest reduction in the overall clinical Juvenile Arthritis Disease Activity Score (cJADAS) and a 17% reduction in the disparity gap between Black and White patients, according to a study presented at the annual meeting of the American College of Rheumatology.

“Our work has led to initial progress in all groups, but we did not fully close the gap in outcomes,” Dori Abel, MD, MSHP, an attending rheumatologist at Children’s Hospital of Philadelphia in Pennsylvania, told attendees. But the project still revealed that it’s feasible to improve outcomes and reduce disparities with a “multipronged, equity-driven approach,” she said. “Stratifying data by demographic variables can reveal important differences in health care delivery and outcomes, catalyzing improvement efforts.”

Giya Harry, MD, MPH, MSc, an associate professor of pediatric rheumatology at Wake Forest University School of Medicine in Winston-Salem, North Carolina, was not involved in the study but praised both the effort and the progress made.

“The results are promising and suggest that with additional interventions targeting other key drivers, the team may be successful in completely eliminating the disparity in outcomes,” Harry said in an interview. “I applaud the hard work of Dr Abel and the other members of the team for doing the important work of characterizing the very complex issue of disparities in JIA outcomes across different race groups.” 

It will now be important to build upon what the physicians learned during this process, said Harry, also the chair of the Diversity, Equity, Inclusion, and Accessibility committee of the Childhood Arthritis and Rheumatology Research Alliance.

“Patience is needed as they cycle through interventions with an emphasis on other key drivers” of disparities, Harry said.

 

Targeting Factors That Clinicians Can Potentially Influence

In her presentation, Abel discussed the various barriers that interfere with patients’ ability to move up the “JIA escalator” of getting referred and diagnosed, starting treatment and getting control of the disease, and monitoring and managing the disease and flares. These barriers include difficulties with access, trust, finances, insurance, caregivers’ missed work, medication burden, side effects, system barriers, and exhaustion and depression among caregivers and patients.

These barriers then contribute to disparities in JIA outcomes. In the STOP-JIA study, for example, Black children had greater polyarthritis disease activity in the first year and greater odds of radiographic damage, Abel noted. At her own institution, despite a mean cJADAS of 2.9 for the whole population of patients with JIA, the average was 5.0 for non-Hispanic Black patients, compared with 2.6 for non-Hispanic White patients.

The team therefore developed and implemented a quality improvement initiative aimed at improving the overall mean cJADAS and narrowing the gap between Black and White patients. The goal was to reduce the mean cJADAS to 2.7 by July 2024 and simultaneously reduce the cJADAS in Black patients by 1.2 units, or 50% of the baseline disparity gap, without increasing the existing gap.

The team first explored the many overlapping and interacting drivers of disparities within the realms of community characteristics, JIA treatment course, patient/family characteristics, organizational infrastructure, divisional infrastructure, and provider characteristics. While many of the individual factors driving disparities are outside clinicians’ control, “there are some domains clinicians may be able to directly influence, such as provider characteristics, JIA treatment course, and possibly divisional infrastructure,” Harry noted, and the team appeared to choose goals that fell under domains within clinicians’ potential influence.

The research team focused their efforts on four areas: Consistent outcome documentation, application of JIA best practices, providing access to at-risk patients, and team awareness and agency.

As part of improving consistent outcome documentation, they integrated outcome metrics into data visualization tools so that gaps were more evident. Applying JIA best practices included standardizing their approach to assessing medication adherence and barriers, with changes to the JIA note templates in the electronic health record and updates to medication adherence handouts.

Providing access to at-risk patients included several components:

• Creating a population management team
• Defining a target population to engage with for earlier follow-up
• Using a monthly batch outreach to defined patients
• Having a coordinator or social worker reach out to those who don’t make appointments
• Using a new JIA/high disease activity video follow-up program.

Finally, team awareness and agency involved giving physicians monthly access to mean cJADAS values for their own patients and at the division level. They also held quarterly disparity mitigation workshops.

Although the institution’s JIA population grew 13%, from 776 to 878 patients, over the course of the study, from January 2023 to May 2024, there was minimal change in the characteristics of the patient population. By May 2024, two thirds of patients (68%) were women, and 23% had public insurance. The population included 67% non-Hispanic White, 9% Hispanic/Latino, 7% non-Hispanic Black, and 4% Asian patients.

One third of the patients (32%) had the oligoarticular subtype, and other subtypes included enthesitis-related at 16%, polyarticular rheumatoid factor (RF)–negative at 15%, systemic at 7%, psoriatic at 6%, undifferentiated at 5%, and polyarticular RF-positive at 4%; data on subtype were unavailable for 14%. Most of their patients (71%) were in a high or very high quintile of the Childhood Opportunity Index, and 12% were in a low or very low quintile.

 

Results of the Quality Improvement Project

As of May 2024, the team had reached most of the goals they had set in terms of individual metrics. They met their goal of having a complete cJADAS calculated in more than 80% of JIA visits each month. With a goal of having over 90% of JIA monthly visits include disease activity target attestations, they reached 95% by May.

They aimed to have over half of JIA monthly visits include documentation of medication adherence/barrier assessment, and 75% of monthly visits had one. For their monthly outreach goal for overdue visits, they aimed to contact more than 75% of patients within 30 days if they were newly overdue for a follow-up visit but had only reached 47% by May 2024. The team had also completed 154 Maintenance of Certification assessments by May.

From initiation of project planning in January 2023 through May 2024, the overall JIA patient population experienced an improvement in cJADAS from 2.9 to 2.54. In individual cJADAS components, the mean patient global score improved from 1.71 to 1.47, the physician global score improved from 0.81 to 0.75, and the joint count score improved from 0.71 to 0.68.

In the non-Hispanic Black population, the mean cJADAS improved from 5.06 in January 2023 to 4.31 in May 2024. Mean cJADAS in the non-Hispanic White population fell from 2.63 to 2.29. With a difference of 0.4 points fewer between the Black and White populations, the disparity gap closed by 17%.

One of the team’s next steps will be to focus on the Hispanic population in 2024-2025 by optimizing language services, working toward greater family involvement to better understand barriers to care, and ongoing population management.

Abel and Harry had no disclosures. No external funding was noted.

A version of this article appeared on Medscape.com.

WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.

“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.

Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.

Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.

“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”

 

Study Results

The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.

Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.

The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).

There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).

Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).

Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).

Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).

In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).

While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.

Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:

• MMP-7 (P = .001)
• IFN gamma (P = .008)
• CCL11 (P < .0001)
• CCL17 (P = .002)
• CCL15 (P < .0001)
• MCP-1 (P = .0003)
• MCP-3 (P = .02)
• CCL25 (P < .0001)
• CD25 (P < .0001)
• GDF-15 (P < .0001)
• TRAIL (P < .0001)
• IL-23 (P = .002)

They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.

The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.

The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.

 

A version of this article appeared on Medscape.com.

WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.

“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.

Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.

Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.

“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”

 

Study Results

The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.

Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.

The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).

There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).

Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).

Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).

Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).

In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).

While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.

Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:

• MMP-7 (P = .001)
• IFN gamma (P = .008)
• CCL11 (P < .0001)
• CCL17 (P = .002)
• CCL15 (P < .0001)
• MCP-1 (P = .0003)
• MCP-3 (P = .02)
• CCL25 (P < .0001)
• CD25 (P < .0001)
• GDF-15 (P < .0001)
• TRAIL (P < .0001)
• IL-23 (P = .002)

They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.

The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.

The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.

 

A version of this article appeared on Medscape.com.

WASHINGTON — Children who have systemic juvenile idiopathic arthritis with lung disease (sJIA-LD) have distinct biomarker profiles that may hold potential in eventually detecting LD earlier and identifying personalized treatment, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

Established risk factors for LD, which affects up to 1 in every 20 patients with sJIA, include being of a younger age, having more macrophage activation syndrome (MAS) episodes, and having more adverse reactions to biologics, Esraa Eloseily, MD, MS, an assistant professor of pediatrics at UT Southwestern Children’s Medical Center, Dallas, told attendees.

“The pathophysiology remains unclear and debate centers around elevated IL-18 [interleukin 18] and T-cell activation in association with HLA-DRB1*15/DRESS [drug reaction with eosinophilia and systemic symptoms] reactions to biologics, and thus, we have urgent unmet needs to understand the prevalence, the pathogenesis, disease biomarkers, and influence of biologics,” Eloseily said.

Their study confirmed that patients with LD tended to be younger and have more MAS. The researchers also found lower hemoglobin and higher white blood cell counts and platelets in patients with sJIA-LD, as well as a higher medication burden, particularly with steroids, biologics, and Janus kinase (JAK) inhibitors.

Randy Cron, MD, PhD, director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham, attended the presentation and noted that every additional piece of information is helpful in filling out the picture of what we know and can predict about sJIA-LD development.

“We’re all learning as we go, so the more people that study this, the better,” Cron told Medscape Medical News. “Even if it’s just seeing things that other groups have seen or really solidifying the risk factors for the development of lung disease, I think, at this point, that’s one of the most clinically relevant things: Do we screen? Who do we screen? Certainly, kids who have very young age of onset, children who develop macrophage activation syndrome, children who have high IL-18 levels.”

 

Study Results

The study compared 37 patients with sJIA-LD from 16 Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry sites with 141 patients with sJIA but without LD who had similar follow-up durations in the CARRA Registry.

Disease duration for patients with sJIA-LD was defined as the time from their initial sJIA diagnosis to their baseline sJIA-LD cohort visit, which was considered their index visit. In patients without LD, duration was from their enrollment in the CARRA Registry to their last CARRA Registry visit, which was considered their index visit.

The patients with sJIA-LD were significantly younger — a median age of 1 year — at onset of sJIA than those without LD, who had a median age of 5 years (P < .0019). The patients with sJIA-LD were also younger (median age, 7 years) at their index visit than those without LD (median age, 10 years) (P < .0001).

There were also significant differences in medication usage between those with and without LD. While 40.5% of patients with sJIA-LD were using steroids at their index visit, only 11.4% of those without LD were using steroids (P < .0001). Yet the mean dose of steroids was significantly lower in those with LD (5.45 mg/d) than in those without (20.7 mg/d). In addition, nearly half the patients with sJIA-LD had ever used cyclosporin A (45.7%) compared with 2.8% of those without LD (P < .0001), and 17.1% of patients with sJIA-LD had used mycophenolate mofetil compared with 0.7% of those without LD (P = .0002).

Similar disparities were seen for usage of biologics and JAK inhibitors: Anakinra (82.9% vs 56.7%; P = .0036), abatacept (8.6% vs 1.4%; P = .053), tofacitinib (57.1% vs 5.7%; P < .0001), ruxolitinib (25.7% vs 0%; P < .0001), baricitinib (8.6% vs 0%; P = .007), and emapalumab (23% vs 0.7%; P < .0001). Further, 5.7% of those with sJIA-LD had taken etoposide and 22.9% had received intravenous immunoglobulin compared with 0% and 4.3%, respectively, in those without LD (P = .04 and P = .001).

Laboratory parameters of patients with sJIA-LD were also significantly different from those of patients without LD, including a higher white blood cell count (8.8 × 109/L vs 8.1 × 109/L; P = .01), higher platelets (316.5 × 109/L vs 311.2 × 109/L; P = .03), and lower hemoglobin (11.5 g/dL vs 12.6 g/dL; P = .007). Ferritin levels trended nonsignificantly higher in patients with sJIA-LD (506 ng/mL vs 173.2 ng/mL; P = .09), and aspartate aminotransferase levels were significantly higher (37 U/L vs 28.72 U/L; P < .0001).

Patients’ overall well-being was “unexpectedly” higher in patients with sJIA-LD (P = .007), Eloseily noted, including the parent/patient rating (P = .027). However, more of the patients without LD had an excellent (61%) or very good (20.4%) health-related quality of life compared with those with LD (13% and 39%), and nearly one third of patients with sJIA-LD (30.4%) had only fair health-related quality of life compared with 5.5% without LD (P = .0002).

In line with known risk factors, most of the patients with sJIA-LD had a prior MAS episode (67.6%) compared with 10.6% of those without LD (P < .0001). Mortality was also higher in those with LD, two of whom died, whereas none without LD died (P = .04).

While existing biomarkers have been reported, they lack independent validation, Eloseily told attendees. Among the known key biomarkers are IL-18/interferon (IFN)-gamma axis, which are known to drive MAS and pulmonary inflammation, especially in those with MAS and LD; ICAM-5 and MMP-7, which is linked to fibrosis and tissue remodeling; and CCL11, CCL17, and GDF-15, which is linked to fibrosis and inflammation.

Because the CARRA Registry has limited availability of biosamples for most patients, the researchers used plasma samples from the FROST study for 27 patients with sJIA-LD and 46 patients without LD. When they compared 23 biomarkers between the groups, most of the known key biomarkers, as well as several other biomarkers, were significantly elevated in those with LD compared with in those without:

• MMP-7 (P = .001)
• IFN gamma (P = .008)
• CCL11 (P < .0001)
• CCL17 (P = .002)
• CCL15 (P < .0001)
• MCP-1 (P = .0003)
• MCP-3 (P = .02)
• CCL25 (P < .0001)
• CD25 (P < .0001)
• GDF-15 (P < .0001)
• TRAIL (P < .0001)
• IL-23 (P = .002)

They found that IL-18 only trended higher (P = .07), and there were not adequate data for ICAM-5.

The study was limited by the differences in disease duration between the compared groups and the limited availability of biosamples, which they only had from patients enrolled in the FROST study.

The research was funded by CARRA and the Arthritis Foundation. Eloseily reported no disclosures. Cron reported serving as an adviser for AbbVie/Abbott and Sobi, receiving grant funding and speaking and consulting fees from Pfizer, and receiving royalties from Springer.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An investigational 12-protein panel of urinary biomarkers predicted histologically active lupus nephritis (LN) with 86% accuracy, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

The noninvasive biomarker panel “robustly predicts meaningful and actionable histological findings” in patients with active proliferative LN, Andrea Fava, MD, assistant professor of medicine in the Division of Rheumatology at Johns Hopkins Medicine in Baltimore, told attendees.

“In contrast to proteinuria, which can’t differentiate inflammation from damage, this panel for histological activity includes a set of 12 proteins linked to intrarenal inflammation,” said Fava, director of Lupus Translational Research at Johns Hopkins. A decline in the biomarker score at 3 months predicted a clinical response at 1 year, and persistent elevation of the score at 1 year predicted permanent loss of kidney function, “which makes it tempting as a treatment endpoint,” Fava said. “Upon further validation, this biomarker panel could aid in the diagnosis of lupus nephritis and guide treatment decisions.” 

Alfred Kim, MD, PhD, an associate professor of medicine at Washington University in St. Louis, was not involved in the research but noted the potential value of a reliable biomarker panel.

“If we have urinary biomarkers that strongly associate with histologic activity, this would be a game changer in the management of LN,” Kim told Medscape Medical News. “Right now, the gold standard is to perform another kidney biopsy to determine if therapy is working. But this is invasive, and many patients do not want to do another kidney biopsy. Conversely, the easiest way to assess lupus nephritis activity is through a urinalysis, focusing on urinary protein levels,” but relying on proteinuria has limitations as well.

“The most important [limitation] is that proteinuria cannot distinguish treatable inflammation from chronic damage,” Fava said. Persistent histologic activity in patients without proteinuria predicts flares, but tracking histologic activity, as Kim noted, requires repeat biopsies.

“So we need better biomarkers because biomarkers that can reflect tissue biology in real time can guide personalized treatment, and that’s one of the main goals of the Accelerating Medicines Partnership [AMP],” he said. The AMP is a public-private partnership between the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), multiple biopharmaceutical and life science companies, and nonprofit and other organizations. Lupus is one of the AMP’s funded projects.

Kim agreed that “effective biomarkers are a huge unmet need in LN.” Further, he said, “imagine a world where the diagnosis of LN can be made just through urinary biomarkers and obviate the need for biopsy. Both patients and providers will be ecstatic at this possibility.” 

Fava described the background for how his research team determined what biomarkers to test. They had previously enrolled 225 patients with LN undergoing a clinically indicated kidney biopsy and collected urine samples from them at baseline and at 12, 24, and 52 weeks after their biopsy.

Of the 225 patients included, 9% with only mesangial LN (class I-II), 25% with pure membranous LN (class V), 24% with mixed LN (class III or IV with or without V), 38% with proliferative LN (class III or IV), and 4% with advanced sclerosis LN (class VI). From these samples, they quantified 1200 proteins and looked at how they correlated with histologic activity.

“What was interesting was that in patients who were classified as responders after 1 year, there were many of these proteins that declined as early as 3 months, suggesting that effective immunosuppression is reducing intrarenal inflammation, and we can capture it in real time,” Fava said.

 

Biomarker Panel Predicts Histologically Active LN

So they set to determining whether they could develop a urinary biomarker for histologically active LN that could be useful in clinical decision-making. They focused on one that could detect active proliferative LN with an NIH activity index score > 2. Their 179 participants included 47.5% Black, 27.9% White, and 14.5% Asian participants, with 10.1% of other races. The predominantly female (86.6%) cohort had an average age of 37 years. Among the LN classes, about one third (34.6%) had pure proliferative disease, 17.9% had mixed proliferative, 27.9% had pure membranous, 11.7% had class I or II, and 5% had class VI. Just over half the participants (55.7%) had not responded to treatment at 12 months, whereas 25% had a complete response, and 19.3% had a partial response.

However, both the 78 participants with an NIH activity index score > 2 and the 101 with a score ≤ 2 had a median score of 3 on the NIH chronicity index. And the urine protein-to-creatinine ratio — 2.8 in the group with an NIH activity index score > 2 and 2.4 in the other group — was nearly indistinguishable between the two groups, Fava said.

They then trained multiple algorithms on 80% of the data to find the best performing set of proteins (with an area under the curve [AUC] of 90%) for predicting an NIH activity index score > 2. They reduced the number of proteins to maximize practicality and performance of the panel, Fava said, and ultimately identified a 12-protein panel that was highly predictive of an NIH activity index score > 2. Then, they validated that panel using the other 20% of the data. The training set had an AUC of 90%, and the test set was validated with an AUC of 93%.

The 12-protein panel score outperformed anti-dsDNA, C3 complement, and proteinuria, with a sensitivity of 81%, a specificity of 90%, a positive predictive value of 87%, a negative predictive value of 86%, and an accuracy of 86%. The proteins with the greatest relative importance were CD163, cathepsin S, FOLR2, and CEACAM-1.

“In contrast to proteinuria, these proteins were related to inflammatory processes found in the kidneys in patients with lupus nephritis, such as activation of macrophages, neutrophils and monocytes, lymphocytes, and complement,” Fava said.

When they looked at the trajectories of the probabilities from the biomarker panel at 3, 6, and 12 months, the probability of the NIH activity index score remaining > 2 stayed high in the nonresponders over 1 year, but the trajectory declined at 3 months in the responders, indicating a decrease in kidney inflammation (P < .001).

 

Can the Biomarker Panel Serve as a Treatment Endpoint?

Then, to determine whether the panel could act as a reliable treatment endpoint, the researchers followed the patients for up to 7 years. One third of the patients lost more than 40% of their kidney function during the follow-up. They found that a high urinary biomarker score at 12 months predicted future glomerular filtration rate loss, independent of proteinuria.

This panel was tested specifically for proliferative LN, so “we may need distinct panels for each [LN type] to capture most of these patients,” Kim said. “I think that’s where the gold mine is: A personalized medicine approach where a large biomarker panel identifies which smaller panel that patient best fits, then use that for monitoring.”

Kim did note an important potential limitation in the study regarding how samples are used in biomarker discovery and validation vs in clinical practice. “Most samples in research studies are frozen, then thawed, while urine is assayed within a couple hours after collection in the clinical setting,” he said. “Do sample processing differences create a situation where a biomarker works in a research project but not in the clinical setting?” But more likely, he said, the opposite may be the case, where frozen samples allow for more degradation of proteins and potentially useful LN biomarker candidates are never detected.

Another challenge, Kim added, albeit unrelated to the study findings, is that diagnostic companies are finding it difficult to get payers to cover new tests, so that could become a challenge if the panel undergoes further validation and then FDA qualification.

The research was funded by Exagen. Fava reported disclosures with Arctiva, AstraZeneca, Exagen, Novartis, UCB, Bristol Myers Squibb, Annexon Bio, and Bain Capital. His coauthors reported financial relationships with numerous pharmaceutical and life science companies, including Exagen, and some are employees of Exagen.

Kim reported research agreements with AstraZeneca, Bristol Myers Squibb, Novartis, and CRISPR Therapeutics; receiving royalties from Kypha; and receiving consulting/speaking fees from AbbVie, Amgen, Atara Bio, Aurinia, Cargo Tx, Exagen, GlaxoSmithKline, Hinge Bio, Kypha, and UpToDate.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An investigational 12-protein panel of urinary biomarkers predicted histologically active lupus nephritis (LN) with 86% accuracy, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

The noninvasive biomarker panel “robustly predicts meaningful and actionable histological findings” in patients with active proliferative LN, Andrea Fava, MD, assistant professor of medicine in the Division of Rheumatology at Johns Hopkins Medicine in Baltimore, told attendees.

“In contrast to proteinuria, which can’t differentiate inflammation from damage, this panel for histological activity includes a set of 12 proteins linked to intrarenal inflammation,” said Fava, director of Lupus Translational Research at Johns Hopkins. A decline in the biomarker score at 3 months predicted a clinical response at 1 year, and persistent elevation of the score at 1 year predicted permanent loss of kidney function, “which makes it tempting as a treatment endpoint,” Fava said. “Upon further validation, this biomarker panel could aid in the diagnosis of lupus nephritis and guide treatment decisions.” 

Alfred Kim, MD, PhD, an associate professor of medicine at Washington University in St. Louis, was not involved in the research but noted the potential value of a reliable biomarker panel.

“If we have urinary biomarkers that strongly associate with histologic activity, this would be a game changer in the management of LN,” Kim told Medscape Medical News. “Right now, the gold standard is to perform another kidney biopsy to determine if therapy is working. But this is invasive, and many patients do not want to do another kidney biopsy. Conversely, the easiest way to assess lupus nephritis activity is through a urinalysis, focusing on urinary protein levels,” but relying on proteinuria has limitations as well.

“The most important [limitation] is that proteinuria cannot distinguish treatable inflammation from chronic damage,” Fava said. Persistent histologic activity in patients without proteinuria predicts flares, but tracking histologic activity, as Kim noted, requires repeat biopsies.

“So we need better biomarkers because biomarkers that can reflect tissue biology in real time can guide personalized treatment, and that’s one of the main goals of the Accelerating Medicines Partnership [AMP],” he said. The AMP is a public-private partnership between the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), multiple biopharmaceutical and life science companies, and nonprofit and other organizations. Lupus is one of the AMP’s funded projects.

Kim agreed that “effective biomarkers are a huge unmet need in LN.” Further, he said, “imagine a world where the diagnosis of LN can be made just through urinary biomarkers and obviate the need for biopsy. Both patients and providers will be ecstatic at this possibility.” 

Fava described the background for how his research team determined what biomarkers to test. They had previously enrolled 225 patients with LN undergoing a clinically indicated kidney biopsy and collected urine samples from them at baseline and at 12, 24, and 52 weeks after their biopsy.

Of the 225 patients included, 9% with only mesangial LN (class I-II), 25% with pure membranous LN (class V), 24% with mixed LN (class III or IV with or without V), 38% with proliferative LN (class III or IV), and 4% with advanced sclerosis LN (class VI). From these samples, they quantified 1200 proteins and looked at how they correlated with histologic activity.

“What was interesting was that in patients who were classified as responders after 1 year, there were many of these proteins that declined as early as 3 months, suggesting that effective immunosuppression is reducing intrarenal inflammation, and we can capture it in real time,” Fava said.

 

Biomarker Panel Predicts Histologically Active LN

So they set to determining whether they could develop a urinary biomarker for histologically active LN that could be useful in clinical decision-making. They focused on one that could detect active proliferative LN with an NIH activity index score > 2. Their 179 participants included 47.5% Black, 27.9% White, and 14.5% Asian participants, with 10.1% of other races. The predominantly female (86.6%) cohort had an average age of 37 years. Among the LN classes, about one third (34.6%) had pure proliferative disease, 17.9% had mixed proliferative, 27.9% had pure membranous, 11.7% had class I or II, and 5% had class VI. Just over half the participants (55.7%) had not responded to treatment at 12 months, whereas 25% had a complete response, and 19.3% had a partial response.

However, both the 78 participants with an NIH activity index score > 2 and the 101 with a score ≤ 2 had a median score of 3 on the NIH chronicity index. And the urine protein-to-creatinine ratio — 2.8 in the group with an NIH activity index score > 2 and 2.4 in the other group — was nearly indistinguishable between the two groups, Fava said.

They then trained multiple algorithms on 80% of the data to find the best performing set of proteins (with an area under the curve [AUC] of 90%) for predicting an NIH activity index score > 2. They reduced the number of proteins to maximize practicality and performance of the panel, Fava said, and ultimately identified a 12-protein panel that was highly predictive of an NIH activity index score > 2. Then, they validated that panel using the other 20% of the data. The training set had an AUC of 90%, and the test set was validated with an AUC of 93%.

The 12-protein panel score outperformed anti-dsDNA, C3 complement, and proteinuria, with a sensitivity of 81%, a specificity of 90%, a positive predictive value of 87%, a negative predictive value of 86%, and an accuracy of 86%. The proteins with the greatest relative importance were CD163, cathepsin S, FOLR2, and CEACAM-1.

“In contrast to proteinuria, these proteins were related to inflammatory processes found in the kidneys in patients with lupus nephritis, such as activation of macrophages, neutrophils and monocytes, lymphocytes, and complement,” Fava said.

When they looked at the trajectories of the probabilities from the biomarker panel at 3, 6, and 12 months, the probability of the NIH activity index score remaining > 2 stayed high in the nonresponders over 1 year, but the trajectory declined at 3 months in the responders, indicating a decrease in kidney inflammation (P < .001).

 

Can the Biomarker Panel Serve as a Treatment Endpoint?

Then, to determine whether the panel could act as a reliable treatment endpoint, the researchers followed the patients for up to 7 years. One third of the patients lost more than 40% of their kidney function during the follow-up. They found that a high urinary biomarker score at 12 months predicted future glomerular filtration rate loss, independent of proteinuria.

This panel was tested specifically for proliferative LN, so “we may need distinct panels for each [LN type] to capture most of these patients,” Kim said. “I think that’s where the gold mine is: A personalized medicine approach where a large biomarker panel identifies which smaller panel that patient best fits, then use that for monitoring.”

Kim did note an important potential limitation in the study regarding how samples are used in biomarker discovery and validation vs in clinical practice. “Most samples in research studies are frozen, then thawed, while urine is assayed within a couple hours after collection in the clinical setting,” he said. “Do sample processing differences create a situation where a biomarker works in a research project but not in the clinical setting?” But more likely, he said, the opposite may be the case, where frozen samples allow for more degradation of proteins and potentially useful LN biomarker candidates are never detected.

Another challenge, Kim added, albeit unrelated to the study findings, is that diagnostic companies are finding it difficult to get payers to cover new tests, so that could become a challenge if the panel undergoes further validation and then FDA qualification.

The research was funded by Exagen. Fava reported disclosures with Arctiva, AstraZeneca, Exagen, Novartis, UCB, Bristol Myers Squibb, Annexon Bio, and Bain Capital. His coauthors reported financial relationships with numerous pharmaceutical and life science companies, including Exagen, and some are employees of Exagen.

Kim reported research agreements with AstraZeneca, Bristol Myers Squibb, Novartis, and CRISPR Therapeutics; receiving royalties from Kypha; and receiving consulting/speaking fees from AbbVie, Amgen, Atara Bio, Aurinia, Cargo Tx, Exagen, GlaxoSmithKline, Hinge Bio, Kypha, and UpToDate.

 

A version of this article appeared on Medscape.com.

WASHINGTON — An investigational 12-protein panel of urinary biomarkers predicted histologically active lupus nephritis (LN) with 86% accuracy, according to research presented at the American College of Rheumatology (ACR) 2024 Annual Meeting.

The noninvasive biomarker panel “robustly predicts meaningful and actionable histological findings” in patients with active proliferative LN, Andrea Fava, MD, assistant professor of medicine in the Division of Rheumatology at Johns Hopkins Medicine in Baltimore, told attendees.

“In contrast to proteinuria, which can’t differentiate inflammation from damage, this panel for histological activity includes a set of 12 proteins linked to intrarenal inflammation,” said Fava, director of Lupus Translational Research at Johns Hopkins. A decline in the biomarker score at 3 months predicted a clinical response at 1 year, and persistent elevation of the score at 1 year predicted permanent loss of kidney function, “which makes it tempting as a treatment endpoint,” Fava said. “Upon further validation, this biomarker panel could aid in the diagnosis of lupus nephritis and guide treatment decisions.” 

Alfred Kim, MD, PhD, an associate professor of medicine at Washington University in St. Louis, was not involved in the research but noted the potential value of a reliable biomarker panel.

“If we have urinary biomarkers that strongly associate with histologic activity, this would be a game changer in the management of LN,” Kim told Medscape Medical News. “Right now, the gold standard is to perform another kidney biopsy to determine if therapy is working. But this is invasive, and many patients do not want to do another kidney biopsy. Conversely, the easiest way to assess lupus nephritis activity is through a urinalysis, focusing on urinary protein levels,” but relying on proteinuria has limitations as well.

“The most important [limitation] is that proteinuria cannot distinguish treatable inflammation from chronic damage,” Fava said. Persistent histologic activity in patients without proteinuria predicts flares, but tracking histologic activity, as Kim noted, requires repeat biopsies.

“So we need better biomarkers because biomarkers that can reflect tissue biology in real time can guide personalized treatment, and that’s one of the main goals of the Accelerating Medicines Partnership [AMP],” he said. The AMP is a public-private partnership between the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), multiple biopharmaceutical and life science companies, and nonprofit and other organizations. Lupus is one of the AMP’s funded projects.

Kim agreed that “effective biomarkers are a huge unmet need in LN.” Further, he said, “imagine a world where the diagnosis of LN can be made just through urinary biomarkers and obviate the need for biopsy. Both patients and providers will be ecstatic at this possibility.” 

Fava described the background for how his research team determined what biomarkers to test. They had previously enrolled 225 patients with LN undergoing a clinically indicated kidney biopsy and collected urine samples from them at baseline and at 12, 24, and 52 weeks after their biopsy.

Of the 225 patients included, 9% with only mesangial LN (class I-II), 25% with pure membranous LN (class V), 24% with mixed LN (class III or IV with or without V), 38% with proliferative LN (class III or IV), and 4% with advanced sclerosis LN (class VI). From these samples, they quantified 1200 proteins and looked at how they correlated with histologic activity.

“What was interesting was that in patients who were classified as responders after 1 year, there were many of these proteins that declined as early as 3 months, suggesting that effective immunosuppression is reducing intrarenal inflammation, and we can capture it in real time,” Fava said.

 

Biomarker Panel Predicts Histologically Active LN

So they set to determining whether they could develop a urinary biomarker for histologically active LN that could be useful in clinical decision-making. They focused on one that could detect active proliferative LN with an NIH activity index score > 2. Their 179 participants included 47.5% Black, 27.9% White, and 14.5% Asian participants, with 10.1% of other races. The predominantly female (86.6%) cohort had an average age of 37 years. Among the LN classes, about one third (34.6%) had pure proliferative disease, 17.9% had mixed proliferative, 27.9% had pure membranous, 11.7% had class I or II, and 5% had class VI. Just over half the participants (55.7%) had not responded to treatment at 12 months, whereas 25% had a complete response, and 19.3% had a partial response.

However, both the 78 participants with an NIH activity index score > 2 and the 101 with a score ≤ 2 had a median score of 3 on the NIH chronicity index. And the urine protein-to-creatinine ratio — 2.8 in the group with an NIH activity index score > 2 and 2.4 in the other group — was nearly indistinguishable between the two groups, Fava said.

They then trained multiple algorithms on 80% of the data to find the best performing set of proteins (with an area under the curve [AUC] of 90%) for predicting an NIH activity index score > 2. They reduced the number of proteins to maximize practicality and performance of the panel, Fava said, and ultimately identified a 12-protein panel that was highly predictive of an NIH activity index score > 2. Then, they validated that panel using the other 20% of the data. The training set had an AUC of 90%, and the test set was validated with an AUC of 93%.

The 12-protein panel score outperformed anti-dsDNA, C3 complement, and proteinuria, with a sensitivity of 81%, a specificity of 90%, a positive predictive value of 87%, a negative predictive value of 86%, and an accuracy of 86%. The proteins with the greatest relative importance were CD163, cathepsin S, FOLR2, and CEACAM-1.

“In contrast to proteinuria, these proteins were related to inflammatory processes found in the kidneys in patients with lupus nephritis, such as activation of macrophages, neutrophils and monocytes, lymphocytes, and complement,” Fava said.

When they looked at the trajectories of the probabilities from the biomarker panel at 3, 6, and 12 months, the probability of the NIH activity index score remaining > 2 stayed high in the nonresponders over 1 year, but the trajectory declined at 3 months in the responders, indicating a decrease in kidney inflammation (P < .001).

 

Can the Biomarker Panel Serve as a Treatment Endpoint?

Then, to determine whether the panel could act as a reliable treatment endpoint, the researchers followed the patients for up to 7 years. One third of the patients lost more than 40% of their kidney function during the follow-up. They found that a high urinary biomarker score at 12 months predicted future glomerular filtration rate loss, independent of proteinuria.

This panel was tested specifically for proliferative LN, so “we may need distinct panels for each [LN type] to capture most of these patients,” Kim said. “I think that’s where the gold mine is: A personalized medicine approach where a large biomarker panel identifies which smaller panel that patient best fits, then use that for monitoring.”

Kim did note an important potential limitation in the study regarding how samples are used in biomarker discovery and validation vs in clinical practice. “Most samples in research studies are frozen, then thawed, while urine is assayed within a couple hours after collection in the clinical setting,” he said. “Do sample processing differences create a situation where a biomarker works in a research project but not in the clinical setting?” But more likely, he said, the opposite may be the case, where frozen samples allow for more degradation of proteins and potentially useful LN biomarker candidates are never detected.

Another challenge, Kim added, albeit unrelated to the study findings, is that diagnostic companies are finding it difficult to get payers to cover new tests, so that could become a challenge if the panel undergoes further validation and then FDA qualification.

The research was funded by Exagen. Fava reported disclosures with Arctiva, AstraZeneca, Exagen, Novartis, UCB, Bristol Myers Squibb, Annexon Bio, and Bain Capital. His coauthors reported financial relationships with numerous pharmaceutical and life science companies, including Exagen, and some are employees of Exagen.

Kim reported research agreements with AstraZeneca, Bristol Myers Squibb, Novartis, and CRISPR Therapeutics; receiving royalties from Kypha; and receiving consulting/speaking fees from AbbVie, Amgen, Atara Bio, Aurinia, Cargo Tx, Exagen, GlaxoSmithKline, Hinge Bio, Kypha, and UpToDate.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — The addition of the bispecific T-cell engager blinatumomab (Blincyto) to chemotherapy greatly boosted 3-year disease-free survival (DFS) in younger pediatric patients with newly diagnosed, standard-risk B-cell acute lymphoblastic leukemia (B-ALL), in a phase 3 randomized trial. 

Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.

As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”

The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average. 

The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug. 

Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black. 

The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001). 

In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively. 

Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.

“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said. 

“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”

Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said. 

“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy. 

“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said. 

As for method of delivery, Rau said easier-to-deliver formulations are in development. 

Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO — The addition of the bispecific T-cell engager blinatumomab (Blincyto) to chemotherapy greatly boosted 3-year disease-free survival (DFS) in younger pediatric patients with newly diagnosed, standard-risk B-cell acute lymphoblastic leukemia (B-ALL), in a phase 3 randomized trial. 

Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.

As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”

The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average. 

The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug. 

Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black. 

The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001). 

In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively. 

Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.

“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said. 

“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”

Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said. 

“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy. 

“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said. 

As for method of delivery, Rau said easier-to-deliver formulations are in development. 

Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO — The addition of the bispecific T-cell engager blinatumomab (Blincyto) to chemotherapy greatly boosted 3-year disease-free survival (DFS) in younger pediatric patients with newly diagnosed, standard-risk B-cell acute lymphoblastic leukemia (B-ALL), in a phase 3 randomized trial. 

Among pediatric patients with B-ALL followed for a mean of 2.5 years (1.6-3.2 years), 718 patients in the blinatumomab-plus-chemotherapy group had a 3-year DFS of 96.0 ± 1.2%, compared with 87.9 ± 2.1% of the 722 patients in the chemotherapy-only group, researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

“Our results demonstrate that blinatumomab added to chemotherapy represents a new treatment standard for most patients with NCI [National Cancer Institute] standard-risk [B-ALL],” said first author Rachel E. Rau, MD, Seattle Children’s Hospital, University of Washington, during a news briefing.

As Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute, noted in a news briefing: “B-cell ALL is the most common childhood cancer and one of the most treatable. However, some children still relapse following standard chemotherapy treatments and then have a much grimmer outcome.”

The AALL1731 study was initiated in 2019 with a recruitment goal of 2245 participants. The patients were over age 1 and less than 10 years, with an initial white blood cell count of < 50,000/μL and were considered to be standard risk–high or standard risk–average. 

The control group received standard-intensity chemotherapy (standard risk–average patients) or augmented Berlin-Frankfurt-Münster–based chemotherapy (standard risk–high patients). In addition, the blinatumomab groups received two cycles of the drug. 

Randomization was terminated in 2024 at 1440 patients because of the positive results. Patients had a median age of 4.3 years (2.8-6.4), 52.6% were boys, 26% were Hispanic, and 5% were non-Hispanic Black. 

The addition of blinatumomab improved DFS by 61% (hazard ratio, 0.39; 95% CI, 0.24-0.64; P < .0001). 

In the group of standard risk–average patients, 3-year DFS was 97.5±1.3% in the blinatumomab group vs 90.2±2.3% in the control group (HR, 0.33; 95% CI, 0.15-0.69). For standard risk–high patients, 3-year DFS was 94.1 ± 2.5% and 84.8 ± 3.8%, respectively. 

Six deaths occurred in remission, all in standard risk–high patients and none during blinatumomab cycles. Out of first courses of blinatumomab, 0.3% were associated with Grade 3 or higher cytokine release syndrome and 0.7% with seizures.

“We did note higher rates of subsequent sepsis and catheter-related infections in our standard risk–average patients who received blinatumomab,” Rau said. 

“The improvement in disease survival was secondary to significant reduction in bone marrow relapse,” Rau added. “We did not see a similar reduction in the more rare event of an isolated central nervous system relapse. This finding was not surprising given blinatumomab’s known limited activity in the central nervous system.”

Rau noted that there are two challenges in terms of access to blinatumomab: its cost, at about $225,000 per a 2023 report, and its administration. The drug is administered via 4-week-long infusions. “The delivery method is very cumbersome,” she said. 

“These are big problems that are going to take the combined efforts of pediatric oncologist cancer consortia and pharmaceutical industry partners as well as government agencies,” she said. Fortunately, she said, in June 2024 the Food and Drug Administration approved blinatumomab for adult and pediatric patients 1 month and older with CD19-positive Philadelphia chromosome–negative B-ALL in the consolidation phase of multiphase chemotherapy. 

“So it’s relatively easy, at least, to prescribe blinatumomab in the United States for our patients that we feel would benefit from it,” she said. 

As for method of delivery, Rau said easier-to-deliver formulations are in development. 

Rau has disclosed spousal employment (AbbVie), serving on advisory boards (Servier, Jazz), consulting, and receiving honoraria (Jazz). Other study authors report various disclosures including ties with Amgen, the maker of blinatumomab. Dunbar has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Omitting 24-hour urine testing from multiple myeloma response assessments does not compromise accurate tracking of patients’ responses to treatment, a new analysis indicates.

Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.

The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.

“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview. 

“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.

Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials. 

Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.

In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.

The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease. 

Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.

The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings. 

Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both. 

Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102). 

Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.

The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.

Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.

“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”

Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Omitting 24-hour urine testing from multiple myeloma response assessments does not compromise accurate tracking of patients’ responses to treatment, a new analysis indicates.

Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.

The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.

“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview. 

“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.

Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials. 

Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.

In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.

The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease. 

Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.

The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings. 

Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both. 

Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102). 

Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.

The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.

Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.

“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”

Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Omitting 24-hour urine testing from multiple myeloma response assessments does not compromise accurate tracking of patients’ responses to treatment, a new analysis indicates.

Overall, evaluating patients’ responses using urine-free and traditional criteria led to nearly identical assessments. When comparing the two criteria, only 7 of 645 patients evaluated had discordant results.

The findings, presented at the American Society of Hematology (ASH) 2024 Annual Meeting, add weight to the push to drop the requirement to perform routine urine tests from International Myeloma Working Group (IMWG) response criteria for multiple myeloma, said the study’s lead author, Rahul Banerjee, MD, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle.

“International guidelines for multiple myeloma, which haven’t been updated in almost a decade, currently recommend these refrigerated 24-hour urine assessments, which are cumbersome for patients and can create substantial disparities,” Banerjee said in an interview. 

“The international community is actually in the midst of updating its guidelines (I am part of this effort), and our work will hopefully help lead the way for future guidelines that de-emphasize the need for 24-hour urine testing to only a few rare scenarios, such as AL amyloidosis,” Banerjee added.

Urine tests can help detect the presence of abnormal proteins, which can indicate the level of myeloma tumor burden. Performing these tests routinely can help physicians monitor the effectiveness of patients’ treatment in practice and clinical trials. 

Some recent data, however, suggest that dropping urine testing from the response criteria would change the response assessment in fewer than 5% of patients. Still, it’s not clear how urine-free criteria would impact assessments of progression free survival.

In the current study, Banerjee and colleagues performed a secondary analysis of the STaMINA trial. In the original trial, patients were randomized to lenalidomide maintenance, tandem autologous hematopoietic cell transplantation followed by lenalidomide maintenance, or consolidation therapy (lenalidomide, bortezomib, and dexamethasone) followed by lenalidomide maintenance until disease progression.

The secondary analysis included 645 patients from the original trial who were evaluable 56 days following autologous hematopoietic cell transplantation. The analysis looked at patients across all groups, but excluded those with progressive disease, and compared patients’ responses using traditional IMWG criteria, which includes 24-hour urine assessments, and urine-free criteria. Response measurements included complete response, very good partial response, partial response, and stable disease. 

Patients were a median age of 56 years, 41% were female, 17% were Black, and 7% were Hispanic; 26% had light-chain only disease. About half (49%) had received lenalidomide alone, 28% had received post-autologous stem cell transplantation consolidation followed by lenalidomide, and 24% had received tandem transplantation followed by lenalidomide.

The analysis showed that “urine-free response criteria worked just fine in terms of their prognostic value,” Banerjee said while presenting the findings. 

Specifically, the complete response rate was 29.4% using the traditional criteria vs 29.7% using the urine-free criteria. The very good partial response rate was 37.0% with the traditional approach vs 36.6% with the urine-free approach. The partial response rate was 30.7% for both and the stable disease rate was 3.0% for both. 

Achieving a complete response based on the urine-free criteria was highly prognostic for progression-free survival (P = .005) while achieving a very good partial response by either criterion was borderline prognostic for progression-free survival (P = .102). 

Only 1.1% of patients — seven patients altogether — had discordant responses between traditional and urine-free response criteria, Banerjee noted. One patient, for instance, was downgraded from a very good partial response with traditional criteria to a partial response with urine-free criteria “because current response criteria rate urine [as] more important than serum-free light chains,” Banerjee explained. Two other patients who met all other stringent criteria for a complete response but still had urine paraprotein at Day 56 were classified as having a very good partial response using traditional criteria but as a complete response with the urine-free criteria.

The other four patients with discordant results were the most important, Banerjee said. These patients were missing urine protein electrophoresis values, which made them non-evaluable using traditional criteria, but became evaluable when using urine-free criteria. “This is, I think, the bane of our existence, right? We ask our patients to put their blood, soul, sweat, and tears into being in a clinical trial, and then they’re not evaluable,” he said.

Overall, these results strongly support the de-emphasis of 24-hour urine requirements in updated IMWG response criteria, said Banerjee. However, he noted, 24-hour urine testing still has a very important place in the screening process and in patients with monoclonal gammopathy of renal significance or AL amyloidosis.

“This study provides reassurance to those of us already not repeating urine tests that urine testing is unnecessary for tracking responses,” said Manni Mohyuddin, MD, from the Multiple Myeloma Program at Huntsman Cancer Institute and assistant professor at the University of Utah, Salt Lake City. “These assessments aren’t done consistently in practice outside of trials anyway, and I hope that this study will lead to a formal change in criteria and the omission of urine assessments in clinical trials.”

Funding for the study was provided by the National Heart, Lung, and Blood Institute; National Cancer Institute; Alliance for Clinical Trials in Oncology; ECOG-ACRIN Cancer Research Group; and SWOG; and contributions were provided by Celgene and Millennium Pharmaceuticals. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol-Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures, and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi. Mohyuddin has disclosed no personal payments and no consultation for industry. His institution has received research funding from Janssen for his role as a principal investigator on a trial.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Patients with multiple myeloma who receive intravenous immunoglobulin (IVIG) prophylaxis during treatment with teclistamab have fewer infections and better overall survival, compared with those who do not receive IVIG prophylaxis, according to new findings presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.

IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.

“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings. 

The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.

In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted. 

Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.

IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.

After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival. 

However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival. 

The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.

A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.

“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.

Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”

Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.” 

Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”

Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Patients with multiple myeloma who receive intravenous immunoglobulin (IVIG) prophylaxis during treatment with teclistamab have fewer infections and better overall survival, compared with those who do not receive IVIG prophylaxis, according to new findings presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.

IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.

“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings. 

The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.

In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted. 

Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.

IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.

After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival. 

However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival. 

The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.

A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.

“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.

Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”

Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.” 

Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”

Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Patients with multiple myeloma who receive intravenous immunoglobulin (IVIG) prophylaxis during treatment with teclistamab have fewer infections and better overall survival, compared with those who do not receive IVIG prophylaxis, according to new findings presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Among 225 consecutive patients who received at least one treatment for relapsed and/or refractory multiple myeloma, those who received IVIG prophylaxis experienced a significantly longer duration of infection-free survival and an almost threefold longer median overall survival, compared with patients who did not receive IVIG prophylaxis.

IVIG supplementation has been shown to prevent severe infections in patients with multiple myeloma, but evidence on the best time to initiate IVIG prophylaxis among those receiving teclistamab remains less clear.

“Our institutional practice is to start IVIG about cycle 2 of therapy, which ended up being around 39 days,” but a key takeaway from the current findings is to “start IVIG within 30 days,” said lead investigator Heloise Cheruvalath, BA, a medical student at Medical College of Wisconsin, Milwaukee, who presented the findings. 

The 225 patients included in the study had received at least one dose of standard-of-care teclistamab or an investigational B-cell maturation antigen (BCMA)–directed bispecific antibody (bsAb). IVIG was given as prophylaxis to 92 patients (41%) in the primary arm. The remaining 133 patients (59%) did not receive IVIG prophylaxis, but 29% received IVIG after a documented infection.

In total, there were 288 infections in 136 patients, and about 61% of infections required hospitalization. Median time to infection was 97 days, with the 12-month cumulative incidence of all-grade infections reaching 73% and the incidence of grade 3 or higher infections totaling 53%. Respiratory tract infections were the most common infection type, with COVID-19 accounting for 11% of cases, Cheruvalath noted. 

Comparing patients who did and did not receive IVIG prophylaxis, median infection-free survival was significantly longer in the prophylaxis group — a median of 7.7 months vs 3 months — as was grade 3 or higher infection-free survival — a median of 14 months vs 7.5 months.

IVIG prophylaxis also led to a higher rate of 2-year progression free survival in the prophylaxis vs nonprophylaxis group — at 38% vs 32% — as well as longer median progression-free survival — at 15 months vs 8 months.

After multivariate analysis, IVIG prophylaxis was no longer significantly associated with improved progression-free survival. 

However, median overall survival did remain significantly better in the IVIG prophylaxis than the nonprophylaxis group after multivariate analysis — 44 months vs 16 months. The presence of high-risk and extramedullary disease was independently associated with worse overall survival. 

The effects of IVIG prophylaxis were stronger for bacterial infections at earlier (30 days or sooner) vs later (31 days or later) time points, but timing of IVIG therapy did not appear to affect the incidence of viral infections.

A study limitation was lack of randomization; IVIG prophylaxis was given at the physician’s discretion. In addition, multiple myeloma treatment was not standardized, with 15% of IVIG patients and 38% of non-IVIG patients receiving investigational BCMA bsAB.

“However, the majority of those who received primary IVIG prophylaxis were treated with standard-of-care teclistamab, making our results generalizable to current clinical practice,” Cheruvalath said.

Rahul Banerjee, MD, who was not involved with the research, noted he has already started providing routine IVIG prophylaxis based on earlier research from this group. “Before I did, my patients would often get very rare infections requiring protracted courses of antibiotics,” Banerjee, from Fred Hutch Cancer Center, University of Washington School of Medicine, Seattle, said in an interview. “Moving to IVIG before the infections start makes much more sense.”

Banerjee also commented that, in general, “the myeloma field has been moving from IV treatments to subcutaneous treatments to lower ‘time toxicity’ and IVIG is a notable exception to that trend, but perhaps it won’t be this way forever.” 

Many patients with rheumatologic conditions receive subcutaneous immunoglobulin, in some cases, with kits they can self-administer at home, Banerjee said, and “I know some groups are starting to work on moving subcutaneous immunoglobulin to the oncologic setting.”

Funding was provided by the Advancing Healthier Wisconsin Endowment. Cheruvalath has reported no relevant disclosures. Banerjee has reported consulting for Adaptive Biotechnologies, Bristol Myers Squibb, Caribou Biosciences, Genentech, GSK, Johnson & Johnson/Janssen, Karyopharm, Legend Biotech, Pfizer, Sanofi, and SparkCures; and receiving research funding from AbbVie, Johnson & Johnson, Novartis, Pack Health, Prothena, and Sanofi.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Compared with clinical trials, a real-world retrospective analysis has linked the bispecific antibodies epcoritamab (Epkinly) and glofitamab (Columvi) to somewhat poorer outcomes in relapsed or refractory large B-cell lymphoma (LBCL).

In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached). 

It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”

He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”

According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”

The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023. 

“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”

The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).

“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.

In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%). 

The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.” 

Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.

“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”

In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”

Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”

In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work. 

“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.” 

He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”

Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.” 

Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”

There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Compared with clinical trials, a real-world retrospective analysis has linked the bispecific antibodies epcoritamab (Epkinly) and glofitamab (Columvi) to somewhat poorer outcomes in relapsed or refractory large B-cell lymphoma (LBCL).

In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached). 

It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”

He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”

According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”

The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023. 

“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”

The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).

“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.

In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%). 

The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.” 

Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.

“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”

In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”

Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”

In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work. 

“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.” 

He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”

Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.” 

Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”

There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Compared with clinical trials, a real-world retrospective analysis has linked the bispecific antibodies epcoritamab (Epkinly) and glofitamab (Columvi) to somewhat poorer outcomes in relapsed or refractory large B-cell lymphoma (LBCL).

In a presentation at the American Society of Hematology (ASH) 2024 Annual Meeting, researchers reported that of 172 patients treated with the drugs who had evaluable responses over a median follow-up of 5 months, median progression-free survival was 2.7 months (95% CI, 2.0-3.9) and median overall survival was 7.2 months (95% CI, 6.1–not reached). 

It’s important to consider the real-world nature of the study’s patient population, said first author Taylor R. Brooks, MD, of Cleveland Clinic, Ohio, in an interview. “Compared to pivotal trials, our cohort was enriched for patients with high-risk features, with almost three quarters having some comorbidity that would’ve excluded them from one of the [earlier] studies.”

He added that “though individuals eligible to receive these medicines may be more sick with high-risk disease, a sizable fraction will respond, and some will maintain remissions.’”

According to Brooks, about one third of patients with diffuse LBCL relapse after standard front-line R-CHOP therapy. “The prognosis is poor for patients who are not candidates for aggressive salvage chemotherapy and for those who relapse after two or more lines,” Brooks said. “T cell–engaging bispecific antibodies have emerged as a promising option for patients with relapsed or refractory large B-cell lymphoma, given their favorable rates and duration of responses as well as their manageable rates of toxicities.”

The Food and Drug Administration (FDA) granted accelerated approval for epcoritamab and glofitamab in 2023. 

“With increasing uptake into clinical practice following the FDA approvals, there is increasing interest in assessing the efficacy and safety of these drugs in real-world, nontrial settings,” Brooks said. “The goal of our study was to investigate outcomes and identify clinical factors associated with outcomes.”

The multicenter, retrospective, observational REALBiTE study tracked 209 patients with relapsed/refractory diffuse LBCL at 19 US centers (epcoritamab, n = 139; glofitamab, n = 70; median age at start of treatment, 67 years [58-76]; 62.2% male; 74.2% diffuse LBCL). The median number of lines of therapy was three (range, 1-12).

“Patients who received epcoritamab tended to be slightly older, were more likely to have a history of indolent non-Hodgkin lymphoma prior to their diagnosis of aggressive B-cell lymphoma and were more likely to have an elevated International Prognostic Index score at the start of bispecific therapy, suggesting that these patients may have been slightly older with higher-risk disease compared to those who received glofitamab,” Brooks said.

In total, 172 patients were response-evaluable. The overall response rate was 50.6% (complete response, 23.8%; partial response, 26.7%; stable disease, 5.8%; progressive disease, 43.6%). 

The overall and complete response rates were “somewhat lower that what has been published in the pivotal trials of these medicines,” Brooks said. The low progression-free and overall survival rates “highlight the difficulty in managing this group of patients.” 

Cytokine release syndrome (CRS) of any grade occurred in 39.2% of patients: 51% in the epcoritamab group and 28.6% in the glofitamab group. Grade ≥3 CRS occurred in 4.3% of patients, who were all taking epcoritamab.

“For epcoritamab, CRS was almost entirely of low grade, and most CRS events occurred around administration of the first full dose of the drug on day 15,” Brooks said. “Similarly, the CRS events for glofitamab were mostly of low grade, though events were observed to occur throughout the step-up dosing. Tocilizumab was administered in about one fifth of the patients.”

In addition, Brooks said, “we found that, among the 19 individuals with paired biopsy samples before and after bispecific therapy, nearly all — 89% — were found to have lost CD20 expression. We expected some patients to experience loss of this important target, but the rate at which we found this to be the case was surprisingly high.”

Brooks added that “clinicians should be acquainted with CRS, ICANS [immune effector cell-associated neurotoxicity syndrome], and mitigation strategies if they are prescribing these medicines. Appropriate and timely management using tocilizumab, steroids, and other adjunctive measures can effectively manage these complications and hopefully allow for the continued delivery of therapy.”

In an interview, Matthew Lunning, DO, associate professor at the University of Nebraska Medical Center/Fred & Pamela Buffett Cancer Center, Omaha, who didn’t take part in the new study, said the findings aren’t bad news. Instead, they’re “practical news,” because they offer insight into how the drugs work. 

“The big lesson from this and other trials is the importance of assessing for CD20 expression prior to taking a bispecific off the shelf, “ he said. “These are learnings that often come after approval.” 

He added that it’s clear that, “in more heavily pretreated patients, more disease led to less optimal results and higher risk for toxicities.”

Lunning also noted that both epcoritamab and glofitamab “entered into a crowded and chaotic relapsed/refractory LBCL space based high complete response rates with the opportunity for durability in those complete responses.” 

Academic institutions were especially interested, as they can manage CRS and ICANS, but “significantly less enthusiasm has been seen in community practices that expect CRS/ICANS to be in the rear-view mirror if they are going to deliver any bispecific,” he said. “It is not that they don’t have the clinical acumen to manage CRS/ICANS. I believe it is the perception of the lack of supportive infrastructure necessary to manage these toxicities.”

There was no study funding. Brooks has reported no disclosures. Other authors have reported various disclosures including relationships with Novartis, AbbVie, Genentech, Genmab, Biogen, Amgen, and others. Lunning has disclosed ties with AbbVie, Genmab, Kite, Bristol-Myers Squibb, Regeneron, and ADC Therapeutics.

A version of this article first appeared on Medscape.com.