B Cell Lymphoma

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

Researchers are calling for the extent of skin erythema to be considered as an outcome measure in patients who develop chronic cutaneous graft-versus-host disease (ccGVHD) after allogeneic stem cell transplants for various blood cancers.

“There is value in collecting erythema serially over time as a continuous variable on a scale of 0%-100%” to identify high-risk patients for prophylactic and preemptive treatment, say investigators led by dermatologist Emily Baumrin, MD, director of the GVHD clinic at the University of Pennsylvania, Philadelphia.

They report a study of more than 300 patients with ccGVHD, which found that the extent of skin erythema strongly predicted the risk for death from GVHD.

Of the 267 patients with cutaneous GVHD at baseline, 103 patients died, the majority without a relapse of their blood cancer.

With additional research, erythema body surface area (BSA) should be “introduced as an outcome measure in clinical practice and trials,” they conclude.

At the moment, the NIH Skin Score is commonly used for risk assessment in cutaneous GVHD, but the researchers found that erythema BSA out-predicts this score.

The investigators explain that the NIH Skin Score does incorporate erythema surface area, but it does so as a categorical variable, not a continuous variable. Among other additional factors, it also includes assessments of skin sclerosis, which the investigators found was not associated with GVHD mortality.

Overall, the composite score waters down the weight given to erythema BSA because the score is “driven by stable sclerotic features, and erythema changes are missed,” they explain.

The study was published online in JAMA Dermatology.
 

Study details

The study included 469 patients with chronic GVHD (cGVHD), of whom 267 (57%) had cutaneous cGVHD at enrollment and 89 (19%) developed skin involvement subsequently.

All of the patients were on systemic immunosuppression for GVHD after allogeneic stem cell transplants for various blood cancers.

They were enrolled from 2007 through 2012 at nine U.S. medical centers – all members of the Chronic Graft Versus Host Disease Consortium – and they were followed until 2018.

Erythema BSA and NIH Skin Score were assessed at baseline and then every 3-6 months. Erythema was the first manifestation of skin involvement in the majority of patients, with a median surface area involvement of 11% at baseline.

The study team found that the extent of erythema at first follow-up visit was associated with both nonrelapse mortality (hazard ratio, 1.33 per 10% BSA increase; P < .001) and overall survival (HR, 1.28 per 10% BSA increase; P < .001), whereas extent of sclerotic skin involvement was not associated with either.

Participants in the study were predominantly White. The investigators note that “BSA assessments of erythema may be less reliable in patients with darker skin.”

The work was funded by the Department of Veterans Affairs and the National Institutes of Health. Dr. Baumrin had no disclosures; one coauthor is an employee of CorEvitas, and two others reported grants/adviser fees from several companies, including Janssen, Mallinckrodt, and Pfizer.

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

Researchers are calling for the extent of skin erythema to be considered as an outcome measure in patients who develop chronic cutaneous graft-versus-host disease (ccGVHD) after allogeneic stem cell transplants for various blood cancers.

“There is value in collecting erythema serially over time as a continuous variable on a scale of 0%-100%” to identify high-risk patients for prophylactic and preemptive treatment, say investigators led by dermatologist Emily Baumrin, MD, director of the GVHD clinic at the University of Pennsylvania, Philadelphia.

They report a study of more than 300 patients with ccGVHD, which found that the extent of skin erythema strongly predicted the risk for death from GVHD.

Of the 267 patients with cutaneous GVHD at baseline, 103 patients died, the majority without a relapse of their blood cancer.

With additional research, erythema body surface area (BSA) should be “introduced as an outcome measure in clinical practice and trials,” they conclude.

At the moment, the NIH Skin Score is commonly used for risk assessment in cutaneous GVHD, but the researchers found that erythema BSA out-predicts this score.

The investigators explain that the NIH Skin Score does incorporate erythema surface area, but it does so as a categorical variable, not a continuous variable. Among other additional factors, it also includes assessments of skin sclerosis, which the investigators found was not associated with GVHD mortality.

Overall, the composite score waters down the weight given to erythema BSA because the score is “driven by stable sclerotic features, and erythema changes are missed,” they explain.

The study was published online in JAMA Dermatology.
 

Study details

The study included 469 patients with chronic GVHD (cGVHD), of whom 267 (57%) had cutaneous cGVHD at enrollment and 89 (19%) developed skin involvement subsequently.

All of the patients were on systemic immunosuppression for GVHD after allogeneic stem cell transplants for various blood cancers.

They were enrolled from 2007 through 2012 at nine U.S. medical centers – all members of the Chronic Graft Versus Host Disease Consortium – and they were followed until 2018.

Erythema BSA and NIH Skin Score were assessed at baseline and then every 3-6 months. Erythema was the first manifestation of skin involvement in the majority of patients, with a median surface area involvement of 11% at baseline.

The study team found that the extent of erythema at first follow-up visit was associated with both nonrelapse mortality (hazard ratio, 1.33 per 10% BSA increase; P < .001) and overall survival (HR, 1.28 per 10% BSA increase; P < .001), whereas extent of sclerotic skin involvement was not associated with either.

Participants in the study were predominantly White. The investigators note that “BSA assessments of erythema may be less reliable in patients with darker skin.”

The work was funded by the Department of Veterans Affairs and the National Institutes of Health. Dr. Baumrin had no disclosures; one coauthor is an employee of CorEvitas, and two others reported grants/adviser fees from several companies, including Janssen, Mallinckrodt, and Pfizer.

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

Researchers are calling for the extent of skin erythema to be considered as an outcome measure in patients who develop chronic cutaneous graft-versus-host disease (ccGVHD) after allogeneic stem cell transplants for various blood cancers.

“There is value in collecting erythema serially over time as a continuous variable on a scale of 0%-100%” to identify high-risk patients for prophylactic and preemptive treatment, say investigators led by dermatologist Emily Baumrin, MD, director of the GVHD clinic at the University of Pennsylvania, Philadelphia.

They report a study of more than 300 patients with ccGVHD, which found that the extent of skin erythema strongly predicted the risk for death from GVHD.

Of the 267 patients with cutaneous GVHD at baseline, 103 patients died, the majority without a relapse of their blood cancer.

With additional research, erythema body surface area (BSA) should be “introduced as an outcome measure in clinical practice and trials,” they conclude.

At the moment, the NIH Skin Score is commonly used for risk assessment in cutaneous GVHD, but the researchers found that erythema BSA out-predicts this score.

The investigators explain that the NIH Skin Score does incorporate erythema surface area, but it does so as a categorical variable, not a continuous variable. Among other additional factors, it also includes assessments of skin sclerosis, which the investigators found was not associated with GVHD mortality.

Overall, the composite score waters down the weight given to erythema BSA because the score is “driven by stable sclerotic features, and erythema changes are missed,” they explain.

The study was published online in JAMA Dermatology.
 

Study details

The study included 469 patients with chronic GVHD (cGVHD), of whom 267 (57%) had cutaneous cGVHD at enrollment and 89 (19%) developed skin involvement subsequently.

All of the patients were on systemic immunosuppression for GVHD after allogeneic stem cell transplants for various blood cancers.

They were enrolled from 2007 through 2012 at nine U.S. medical centers – all members of the Chronic Graft Versus Host Disease Consortium – and they were followed until 2018.

Erythema BSA and NIH Skin Score were assessed at baseline and then every 3-6 months. Erythema was the first manifestation of skin involvement in the majority of patients, with a median surface area involvement of 11% at baseline.

The study team found that the extent of erythema at first follow-up visit was associated with both nonrelapse mortality (hazard ratio, 1.33 per 10% BSA increase; P < .001) and overall survival (HR, 1.28 per 10% BSA increase; P < .001), whereas extent of sclerotic skin involvement was not associated with either.

Participants in the study were predominantly White. The investigators note that “BSA assessments of erythema may be less reliable in patients with darker skin.”

The work was funded by the Department of Veterans Affairs and the National Institutes of Health. Dr. Baumrin had no disclosures; one coauthor is an employee of CorEvitas, and two others reported grants/adviser fees from several companies, including Janssen, Mallinckrodt, and Pfizer.

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

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

A new real-world analysis finds that severe infection rates were higher than in clinical trials in 67 patients with chronic lymphocytic leukemia (CLL) or B-cell lymphoma who took ibrutinib (Imbruvica), idelalisib (Zydelig), or venetoclax (Venclexta).

For example, “the rate of severe infection for ibrutinib in clinical trials ranged from 12.8% to 45% with median follow-up ranging from 27 to 65 months. In our study, the rate of severe infection was 45.3% within a shorter median follow-up period of 23.3 months,” said study lead author Amanda Tey, MPharm, a hematology pharmacist with Monash Health in Clayton, Australia, in an interview.

The results suggest that “real-world severe infection risk is higher than previously appreciated,” said Ms. Tey, whose findings were published in the European Journal of Hematology. “Poor performance status and a high comorbidity burden further increase this risk.”

According to the study, there are limited data about real-world infection rates for patients with CLL or B-cell lymphoma who take the three drugs.

Both the underlying blood cancer and the drugs themselves may disrupt the immune system in these patients, Ms. Tey noted. “Ibrutinib inhibits interleukin-2-inducible T-cell kinase, which has a role in T-cell maturation. Idelalisib reduces regulatory T-cell activity and natural killer cell and neutrophil inflammatory responses. Venetoclax is associated with a high rate of neutropenia.”

For the new retrospective, single-center study, researchers tracked adult patients who’d received the drugs from 2014 to 2021 in a hospital network serving 1.5 million people in the Australian state of Victoria. The primary outcome was severe infection of grade 3 or higher. Patients were excluded for such factors as having been primarily treated at other facilities, receiving less than 30 days of treatment, or having been treated for other indications such as primary central nervous system lymphoma.

Of the 67 patients in the study, the numbers taking the drugs were 53 (ibrutinib), 8 (idelalisib), and 6 (venetoclax). Eleven patients took more than one drug. Median age was 73 years, and 73% of patients were male.

Patients spent a median 23.3, 4.8, and 3.5 months taking ibrutinib, idelalisib, and venetoclax, respectively, before treatment stopped or data were collected. Patients were commonly prescribed antimicrobials to prevent pneumocystis jirovecii pneumonia and herpes simplex virus (HSV)/varicella zoster virus (VZV) infection.

Researchers found that 48% of the patients had at least one serious infection: 45% of those on ibrutinib, 63% of those on idelalisib, and 50% of those on venetoclax. Seven patients died of infections.

In comparison, the researchers reported, a systematic review of idelalisib in blood cancer clinical trials reported an overall infection rate of 28%, while clinical trials reported an infection rate of 17.5%-22% in patients taking venetoclax for CLL.

Poor performance status and higher levels of comorbidity were linked to higher risk of infection, and infections occurred at a median of 5.4 months.

Lead author Ms. Tey highlighted the fact that most of the patients in the new study had relapsed/refractory disease. The infection risk in the real-world first-line setting is unknown, she said. “Furthermore, due to the size of our study and high uptake of antimicrobial prophylaxis, the optimal prophylaxis strategy for these patients remains unclear.”

In an interview, infectious disease physician Gemma Reynolds, MChD, MPH, of Austin Health and Peter MacCallum Cancer Center in Melbourne, said the study findings reflect “a lot of what we know from other observational studies and clinical practice. There is a risk of infection, and serious infection, associated with these agents. Sometimes the pathogen is classically opportunistic, but often it is bacterial, and respiratory sites are common. Infections often occur early into a course of therapy.”

Dr. Reynolds, who didn’t take part in the study, urged colleagues to cast a wide net if a patient appears to have an infection but doesn’t respond to conventional therapies such as antibiotics. “Unusual infections are possible,” she said, and aggressive early workups may be advisable via blood cultures, viral swabs, sputum culture, early imaging, bronchoscopy, and preemptive monitoring in patients with a prior infection history with a disease such as CMV.

Alessandra Ferrajoli, MD, a hematologist/oncologist at MD Anderson Cancer Center who also didn’t take part in the study, agreed in an interview that the findings reflect those found in other reports. “It should be highlighted that the population studied is at particular high risk for infections given the high proportion of patients with recurrent disease (85%), many patients with concurrent hypogammaglobulinemia (64%), and the patient median age of 73 years and a high comorbidities burden,” she said. “In my view, this explains the higher rate of infections reported in this study, when compared to other case series.”

Dr. Ferrajoli added that there’s no standard antimicrobial prophylaxis for patients with B-cell malignancies receiving targeted therapies. “Anti-HSV/VZV prophylaxis is commonly implemented. Additional antiviral, antimicrobial, and antifungal prophylaxis should be used based on patients’ absolute neutrophil and T-cell count and individual risk factors, including prior history of infections such as CMV, prior splenectomy, and history of invasive fungal infections.”

The study was funded by Monash Health, the National Health and Medical Research Council (Australia), and the Society of Hospital Pharmacists of Australia. Ms. Tey reported no disclosures. Some of the study authors reported multiple disclosures. Dr. Reynolds discloses a PhD scholarship from the National Health and Medical Research Council. Dr. Ferrajoli reported no disclosures.

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

One therapy that has transformed the management of this disease is anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. Currently there are three FDA-approved options for patients with relapsed/refractory large B-cell lymphoma (LBCL) who have received at least two prior lines of therapy.^[1-3] More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for second-line therapy on the basis of results of the ZUMA-7 and TRANSFORM studies, respectively.^[4,5]The primary analysis of the TRANSFORM study, which included patients with primary refractory or early relapse of large B-cell lymphoma, is now available. In this study, 184 patients were randomly assigned to receive liso-cel or three cycles of the standard of care (high-dose chemotherapy and autologous stem cell transplantation). After a 17.5-month median follow-up, the liso-cel vs standard-of-care group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low rates of grade 3 cytokine release syndrome (1%) and neurologic events (4%). This confirms the role of liso-cel in the second-line setting for high-risk patients.

Another promising treatment approach across lymphoma subtypes, including DLBCL, are CD20/CD3 bispecific monoclonal antibodies. The results of the phase 2 trial of glofitamab for patients with relapsed/refractory DLBCL were published recently. This study included 155 patients with relapsed/refractory DLBCL after at least two prior lines of therapy. Approximately one third of patients had received prior CAR T-cell therapy. Patients were treated for a fixed duration of 12 cycles. At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. Seventy-eight percent of patients with a complete response continued to be in remission at 12 months. Grade 3 or higher cytokine release syndrome was rare and occurred in less than 5% of patients.

Bispecific antibodies have many advantages, including off-the-shelf access and favorable toxicity profiles. Longer follow-up, however, will be required to determine the durability of response beyond 1 year. As bispecific antibodies become available, many questions will emerge, including how best to sequence with CAR T-cell therapy and whether to combine them with other regimens. Additional studies of bispecific antibodies in combination with chemoimmunotherapy and other treatment approaches are underway.

Additional References

1.         Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. Doi:10.1056/NEJMoa1707447

2.         Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. Doi:10.1056/NEJMoa1804980

3.         Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. Doi:10.1016/S0140-6736(20)31366-0

4.         Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. Doi:10.1056/NEJMoa2116133

5.         Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. Doi:10.1016/S0140-6736(22)00662-6

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Diagnosis to treatment interval (DTI; time in days from the diagnosis date to therapy initiation) is strongly associated with poor survival outcomes in patients with newly diagnosed mantle cell lymphoma (MCL).

Major finding: Patients with a short vs long DTI had significantly shorter median overall (7.8 vs 11.8 years) and progression-free (2.5 vs 4.8 years) survival (both log-rank P < .0001). A short vs long DTI was associated with significantly poorer overall (adjusted hazard ratio [aHR] 1.57) and progression-free (aHR 1.50) survival (both P < .001).

Study details: This pooled analysis of three large datasets included 1097 patients with newly diagnosed MCL and available DTI data, of which 300 had a short (0-14 days) and 797 had a long (15-60 days) DTI.

Disclosures: One of the datasets, Molecular Epidemiology Resource, was supported by grants from the US National Cancer Institute. Some authors reported ties with various organizations.

Source: Epperla N et al. Impact of diagnosis to treatment interval in patients with newly diagnosed mantle cell lymphoma. Blood Adv. 2022 (Dec 14). Doi: 10.1182/bloodadvances.2022009225

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Low natural killer (NK) cell counts (NKCC; <100 cells/μL) at diagnosis predict poor outcomes in patients with diffuse large B-cell lymphoma (DLBCL), and lenalidomide maintenance therapy has no impact on this unfavorable prognosis.

Major finding: Low baseline NKCC were associated with shorter progression-free (hazard ratio [HR] 2.2) and overall (HR 2.8) survival (both P < .001), independently of age-adjusted International Prognostic Index scores, and with a higher risk for progression or relapse (P = .0025). Lenalidomide maintenance therapy did not affect the prognostic value of low NKCC at diagnosis or random assignment (P = .6349).

Study details: This prospective ancillary study of the REMARC trial included 335 elderly patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone who underwent flow cytometric peripheral blood lymphocyte analysis at diagnosis, at random assignment to the lenalidomide or placebo arm, or at 6 months after random assignment.

Disclosures: This study was funded by Celgene. Some authors reported ties with various organizations, including Celgene.

Source: Beldi-Ferchiou A et al. Lenalidomide maintenance fails to overcome the unfavourable prognosis of low NK-cell counts in rituximab–chemotherapy responsive elderly DLBCL patients: A LYSA group study. Br J Haematol. 2023 (Feb 6). Doi: 10.1111/bjh.18642

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640