Lymphoma & Plasma Cell Disorders

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

CHICAGO – A chemotherapy-free regimen has produced promising early response and survival outcomes in patients with a particularly poor-prognosis subtype of diffuse large B-cell lymphoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.

The overall response rate was 86% after two cycles of combined rituximab, lenalidomide, and ibrutinib – or RLI – in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) of the non–germinal center (non-GCB) subtype, said Jason Westin, MD, of the department of lymphoma/myeloma at the University of Texas MD Anderson Cancer Center in Houston.

The response rate increased to 96% after subsequent cycles of RLI plus standard chemotherapy, said Dr.Westin, who added that the rates of progression-free and overall survival at 1 year were also 96% in the investigator initiated, single-arm, open-label, phase 2 study, called Smart Start.

That looks quite favorable, compared with what’s been achieved in previous studies in this poor-prognosis group of patients, Dr. Westin said during a podium presentation of Smart Start data, though he cautioned against direct comparison to historical studies and added that further follow-up is needed.

“Our survival outcomes appear excellent with about a year’s worth of follow-up,” he said during his presentation. “I’d say the novel/novel combinations, with and without chemotherapy, are feasible for large cell, and next step studies are warranted.”

Jasmine M. Zain, MD, of City of Hope Comprehensive Cancer Center, said these results so far raise the possibility of an effective chemotherapy-free treatment regimen for aggressive lymphomas.

“This regimen, particularly for non-GCB subtypes, is extremely promising,” Dr. Zain said during a podium discussion of the study. “I think we were all oohing and aahing over the results, and it could possibly even be practice changing.”

Moving to a nonchemotherapy regimen could raise new questions for treatment of non-GCB and possibly also GCB subtypes of DLBCL, such as when the treatments could be stopped, or whether a maintenance approach would be useful, she added.

The Smart Start study enrolled a total of 60 patients with non-GCB DLBCL. The patients received RLI for two 21-day cycles, followed by another six cycles of RLI plus chemotherapy, which was either EPOCH or CHOP, at the investigators’ discretion.

“With a median follow-up of 362 days, we’ve had three progression events,” Dr. Westin said in his discussion of the preliminary efficacy results.

Adverse events were similar to what would be expected for standard chemotherapy, according to Dr. Westin, except for rash, which was seen mainly in cycles one and two.

There were two deaths on study protocol, including one fatal fungal infection that investigators attributed to high dose corticosteroids and RLI. There were no subsequent fungal infections after a protocol amendment prohibiting corticosteroids during the RLI-only cycles, according to the investigators’ report.

The high response rates following the initial lead-in phase made investigators wonder what would happen without subsequent chemotherapy, Dr. Westin told attendees during his oral presentation. In one case, a 74-year-old man did complete the two lead-in cycles of RLI and declined further therapy.

“He’s now nearly 2 years out, without any additional therapy, and has not relapsed to date,” Dr. Westin said. “This is, again, with 6 weeks worth of RLI therapy.”

Final results and minimal residual disease data from the Smart Start study will be presented at a conference later in 2019, Dr. Westin said.

The study received research support and funding from the ASCO Conquer Cancer Foundation. The trial drug and support were provided by Celgene and Janssen. Dr. Westin reported disclosures related to Celgene, Genentech/Abbvie, Kite Pharma, Kite/Gilead, Novartis, ProNAi, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Janssen, and Karyopharm Therapeutics.

SOURCE: Westin J et al. ASCO 2019, Abstract 7508.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

For patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT), adding daratumumab to lenalidomide and dexamethasone provides better outcomes than standard therapy alone, based on an interim analysis from the phase 3 MAIA trial.

A greater proportion of patients in the daratumumab group had complete responses and were alive without disease progression after a median follow-up of 28 months, reported lead author Thierry Facon, MD, of the University of Lille (France) and colleagues, who also noted that daratumumab was associated with higher rates of grade 3 or 4 pneumonia, neutropenia, and lymphopenia.

“For patients who are ineligible for stem-cell transplantation, multiagent regimens, including alkylating agents, glucocorticoids, immunomodulatory drugs, proteasome inhibitors, and new agents, are the standard of care,” the investigators wrote in the New England Journal of Medicine.

The findings from MAIA add clarity to the efficacy and safety of daratumumab in this setting, building on previous phase 3 myeloma trials in the same area, such as ALCYONE, CASTOR, and POLLUX, the investigators noted.

MAIA was an open-label, international trial involving 737 patients with newly diagnosed multiple myeloma who were ineligible for ASCT. Patients were randomized in a 1:1 ratio to receive either daratumumab, lenalidomide, and dexamethasone (daratumumab group; n = 368) or lenalidomide and dexamethasone alone (control group; n = 369).

On a 28-day cycle, all patients received oral lenalidomide 25 mg on days 1-21 and oral dexamethasone 40 mg on days 1, 8, 15, and 22. Patients in the daratumumab group received intravenous daratumumab dosed at 16 mg/kg once a week for cycles 1 and 2, every 2 weeks for cycles 3-6, and then every 4 weeks thereafter. Treatment was continued until unacceptable toxic effects or disease progression occurred.

The primary end point was progression-free survival (PFS). Various secondary end points were also evaluated, including time to progression, complete responses, overall survival, and others.

Among the 737 randomized patients, 729 ultimately underwent treatment. The median patient age was 73 years.

Generally, efficacy measures favored adding daratumumab. After a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% of patients in the daratumumab group, compared with 38.8% in the control group.

The median PFS was not reached in the daratumumab group, compared with 31.9 months in the control group. There was a 44% lower risk of disease progression or death among patients who received daratumumab, compared with the control group (hazard ratio, 0.56, P less than .001).

This PFS trend was consistent across most subgroups, including those for sex, age, and race, with the exception of patients with baseline hepatic impairment.

Additional efficacy measures added weight to the apparent benefit of adding daratumumab. For instance, more patients in the daratumumab group achieved a complete response or better (47.6% vs. 24.9%) and were negative for minimum residual disease (24.2% vs. 7.3%).

In terms of safety, more patients in the daratumumab group than the control group developed grade 3 or higher neutropenia (50% vs. 35.3%), lymphopenia (15.1% vs. 10.7%), infections (32.1% vs. 23.3%) or pneumonia (13.7% vs. 7.9%).

In contrast, grade 3 or 4 anemia was less common in the daratumumab group than the control group (11.8% vs. 19.7%). Overall, the rate of serious adverse events was similar for both groups (approximately 63%), as was the rate of adverse events resulting in death (approximately 6%-7%).

“In this trial involving patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to lenalidomide and dexamethasone resulted in significantly longer progression-free survival, a higher response rate, an increased depth of response, and a longer duration of response than lenalidomide and dexamethasone alone,” the investigators concluded.

The study was funded by Janssen Research and Development. The investigators reported relationships with Janssen, Celgene, Takeda, Sanofi, and other companies.

SOURCE: Facon T et al. N Engl J Med. 2019;380:2104-15.

The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.

FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).

A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).

The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.

“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.

[email protected]

The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.

FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).

A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).

The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.

“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.

[email protected]

The Food and Drug Administration has approved lenalidomide (Revlimid), in combination with rituximab, for the treatment of adult patients with previously treated follicular or marginal zone lymphoma.

FDA approval is based on results from the randomized, double-blind, phase 3 AUGMENT trial, which evaluated lenalidomide/rituximab versus rituximab and placebo in patients with previously treated follicular or marginal zone lymphoma. The median progression-free survival in those receiving lenalidomide/rituximab was 39.4 months, compared with 14.1 months for those receiving rituximab/placebo (odds ratio, 0.46; 95% confidence interval, 0.34-0.62; P less than .0001).

A numeric trend was seen in overall survival over the follow-up period of 28.3 months (16 vs. 26 deaths; hazard ratio, 0.61; 95% CI, 0.33-1.13).

The most common adverse events associated with lenalidomide/rituximab are neutropenia, diarrhea, constipation, cough, fatigue, rash, pyrexia, leukopenia, pruritus, upper respiratory tract infections, abdominal pain, anemia, headache, and thrombocytopenia. Lenalidomide also contains a boxed warning for embryo-fetal toxicity, hematologic toxicity, and venous and arterial thromboembolism.

“Chemotherapy continues to be a standard of care for indolent forms of NHL, but most patients will relapse or become refractory to their current treatment. This approval represents a new therapeutic option for previously treated patients with follicular and marginal zone lymphomas, including those who relapse or no longer respond to initial treatment,” Meghan Gutierrez, CEO of the Lymphoma Research Foundation, said in a statement.

[email protected]

In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.

“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.

They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.

The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.

After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).

The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.

However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.

In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.

The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.

In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.

“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.

They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.

The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.

After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).

The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.

However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.

In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.

The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.

In a large cohort of patients with mantle cell lymphoma (MCL), CD23 expression was associated with significantly improved survival outcomes, according to a retrospective analysis.

“Mantle cell lymphoma has a distinctive immunophenotype, typically positive for pan B-cell markers, CD5 and cyclin D1, but negative for CD10, CD23, and CD200. Although most cases show this immunophenotype, some MCL cases have atypical immunophenotypic features, such as expression of CD10, CD23, or rarely CD200 or lack of expression of CD5,” wrote Annapurna Saksena, MD, of MD Anderson Cancer Center, Houston, and colleagues. Their report is in Human Pathology.

They retrospectively reviewed medical records from a pathology database at MD Anderson from the period of 2008-2016. In all, 798 patients with MCL were identified, of which 103 were classified as CD23-positive via flow cytometry.

The team collected data related to the immunophenotypic and clinicopathologic characteristics of the disease, in addition to survival-related outcomes, including progression-free survival (PFS) and overall survival (OS). They compared outcomes for the CD23-positive group against 240 patients with CD23-negative MCL.

After analysis, Dr. Saksena and colleagues found that patients with CD23-positive MCL more frequently had bone marrow involvement (89% vs. 78%, P = .02), a leukemic nonnodal presentation (42% vs. 11%, P = .0001), an elevated leukocyte count (33% vs. 18%, P = .009), and stage 4 disease (87% vs. 77%, P = .03).

The researchers reported that CD23 expression was associated with significantly improved PFS and OS (P = .029 and P = .02, respectively) in the univariate analysis.

However, the prognostic significance was partially lost when leukemic nonnodal cases were excluded, the researchers reported.

In addition to the higher frequency of leukemic nonnodal presentation with CD23-positive MCL cases, there was a higher frequency of CD200 expression and a lower frequency of SOX11 expression.

The researchers acknowledged that a key limitation of the study was the loss of prognostic significance in the multivariate analysis. Further studies are needed to fully understand the links between CD23 expression and MCL survival, they noted.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Saksena A et al. Hum Pathol. 2019 May 2. doi: 10.1016/j.humpath.2019.04.010.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.

Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.

In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.

The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.

Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).

“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”

The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.

This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.

[email protected]

SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.

Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.

Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.

In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.

The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.

Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).

“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”

The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.

This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.

[email protected]

SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.

Results from a 13-year follow-up of a trial comparing two types of rituximab-based chemotherapy as upfront treatment for patients with follicular lymphoma show an “extraordinary improvement” in overall survival, compared with the prerituximab era.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

In a finding that the researchers termed “somewhat unexpected,” complete remission was the strongest factor in long-term survival.

Between March 2000 and May 2005, researchers enrolled 136 high-risk follicular lymphoma patients in the GITMO-IIL trial to evaluate the superiority of high-dose chemotherapy with rituximab and autograft (R-HDS) versus conventional chemotherapy with rituximab (R-CHOP) as frontline therapy. At a median follow-up of 4 years, there was no survival advantage for R-HDS.

In the current analysis – that had a 13-year median follow-up – median survival had not yet been reached. As of February 2017, two-thirds of all patients were alive at their last follow-up. Overall survival was 68.5% in the R-CHOP arm and 64.5% in the R-HDS arm, Riccardo Bruna, MD, of the European Institute of Oncology in Milano, Italy, and his colleagues, reported in Haematologica.

The main causes of death for the 46 patients who had died as of long-term follow-up were disease progression and secondary malignancies. Other causes included cardiovascular events, infections, graft failure following autograft, anaphylactic shock, and late sudden death.

Complete remission was seen in 98 patients (73.1%) overall – 59.1% in the R-CHOP arm and 86.7% in the R-HDS arm. Achieving durable complete remission was associated with prolonged survival, the researchers reported. Of the 79 patients in complete remission at 2 years after the start of treatment, 65 (82.3%) were alive at 13 years, compared with 21 (58.3%) of 36 patients who had an early relapse (P = .003).

“[Complete remission] achievement was the most important factor for prolonged survival,” the researchers wrote. “The importance of disease response is further emphasized by the first-time observation that [molecular remission] achievement is associated with survival duration and a high proportion of patients had prolonged survival in the absence of disease recurrence.”

The researchers reported that this is longest ever follow-up reported for first-line treatment of follicular lymphoma with rituximab-based chemotherapy.

This work was supported in part by the Ministero Italiano Università e Ricerca and by Banca del Piemonte. The initial clinical trial was supported by Compagnia di San Paolo, Regione Piemonte, and Roche, which provided rituximab for the study.

[email protected]

SOURCE: Bruna R et al. Haematologica. 2019 Apr 11. doi: 10.3324/haematol.2018.209932.

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

An atypical case of cutaneous mantle cell lymphoma (MCL) with histomorphological features mimicking subcutaneous panniculitis-like T-cell lymphoma (SPTCL) highlights a “potential pitfall,” according to investigators.

This unusual case stresses the importance of molecular cytogenetics and/or immunohistochemistry for panniculitis-type lymphomas, reported lead author Caroline Laggis, MD of the University of Utah, Salt Lake City, and colleagues.

“While morphologic features of SPTCL, specifically rimming of adipocytes by neoplastic lymphoid cells, have been documented in other types of lymphomas, this case is exceptional in that the morphologic features of SPTCL are showed in secondary cutaneous involvement by MCL,” the investigators wrote. Their report is in Journal of Cutaneous Pathology.

The patient was a 69-year-old man who presented with 2-year history of night sweats and fever of unknown origin, and, closer to presentation, weight loss and tender bumps under the skin of his pelvic region.

Subsequent computed tomography and excisional lymph node biopsy led to a diagnosis of MCL, with a Mantle Cell Lymphoma International Prognostic Index of 5, suggesting aggressive, intermediate-risk disease. Further imaging showed involvement of the nasopharynx, and cervical and mediastinal lymph nodes.

Bendamustine and rituximab chemotherapy was given unremarkably until the final cycle, at which point the patient presented with tender subcutaneous nodules on his lower legs. Histopathology from punch biopsies revealed “a dense infiltrate of monomorphic, mitotically active lymphoid cells with infiltration between the deep dermal collagen and the adipocytes in subcutaneous fat,” the investigators wrote, noting that the infiltrative cells were blastoid and 70% expressed cyclin D1, supporting cutaneous involvement of his systemic MCL.

Treatment was switched to ibrutinib and selinexor via a clinical trial, which led to temporary improvement of leg lesions; when the lesions returned, biopsy was performed with the same histopathological result. Lenalidomide and rituximab were started, but without success, and disease spread to the central nervous system.

Another biopsy of the skin lesions again supported cutaneous MCL, with tumor cells rimming individual adipocytes.

Because of this atypical morphology, fluorescence in situ hybridization (FISH) was conducted, revealing t(11;14)(q13:32) positivity, thereby “confirming the diagnosis of cutaneous involvement by systemic MCL,” the investigators wrote.

Genomic sequencing revealed abnormalities of “ataxia-telangiectasia mutated, mechanistic target of rapamycin kinase (mTOR), BCL6 corepressor, and FAS-associated factor 1, as well as the expected mutation in IGH-CCND1, leading to cyclin D1 upregulation.”

Subsequent treatment was unsuccessful, and the patient died from his disease.

“The complex and central role that mTOR plays in adipose homeostasis may link our tumor to its preference to the adipose tissue, although further investigation is warranted regarding specific genomic alterations in lymphomas and the implications these mutations have in the involvement of tumor cells with cutaneous and adipose environments,” the investigators wrote.

The investigators did not report conflicts of interest.

SOURCE: Laggis C et al. 2019 Apr 8. doi:10.1111/cup.13471.

Investigators have identified a mechanism of ibrutinib resistance in mantle cell lymphoma (MCL) and showed that a small molecule can overcome that resistance in vitro and in vivo.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The team found that ibrutinib-resistant MCL cells rely on oxidative phosphorylation (OXPHOS) and glutaminolysis to survive.

Targeting the OXPHOS pathway with a small molecule, IACS-010759, inhibited the proliferation of ibrutinib-resistant cells in vitro.

IACS-010759 also decreased tumor volume and improved survival in mouse models of ibrutinib-resistant MCL and double-hit B-cell lymphoma.

Now, IACS-10759 is being tested in phase 1 trials of lymphoma and solid tumors (NCT03291938) as well as acute myeloid leukemia (NCT02882321).

Liang Zhang, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted the preclinical research and described their findings in Science Translational Medicine.

The investigators sequenced samples from MCL patients with ibrutinib-sensitive and -resistant disease and found that “glutamine-fueled OXPHOS appears to be a prominent energy metabolism pathway in ibrutinib-resistant MCL cells.”

This finding prompted the team to test IACS-010759, an inhibitor of ETC complex I, in ibrutinib-resistant MCL. They theorized that the inhibitor would be effective because, during OXPHOS, electrons are transferred from electron donors to acceptors through the ETC in redox reactions that release energy to form ATP, and OXPHOS generates ATP to meet requirements for cell growth.

In experiments, IACS-010759 inhibited the proliferation of two ibrutinib-resistant MCL cell lines, Z-138 and Maver-1, in a dose-dependent manner.

The investigators also tested IACS-010759 in two mouse models of ibrutinib-resistant MCL. In both models, mice treated with IACS-010759 had a significant reduction in tumor volume, compared with controls. In one model, IACS-010759 extended survival by a median of 11 days.

Finally, the team tested IACS-010759 in a model of ibrutinib-resistant, double-hit (MYC and BCL-2) B-cell lymphoma with central nervous system involvement. Again, IACS-010759 significantly inhibited tumor growth. Compared to ibrutinib and vehicle control, IACS-010759 provided a median survival benefit of more than 20 days.

There were no toxicities associated with IACS-010759 treatment, according to the investigators.

This research was supported by the MD Anderson B Cell Lymphoma Moon Shot Project, Gary Rogers Foundation, Kinder Foundation, Cullen Foundation, Cancer Prevention Research Institute of Texas, and the National Institutes of Health. Most investigators reported having no competing interests, but two reported a patent (WO/2015/130790).

[email protected]

SOURCE: Zhang L et al. Sci Transl Med. 2019 May 8. doi: 10.1126/scitranslmed.aau1167.

Investigators have identified a mechanism of ibrutinib resistance in mantle cell lymphoma (MCL) and showed that a small molecule can overcome that resistance in vitro and in vivo.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The team found that ibrutinib-resistant MCL cells rely on oxidative phosphorylation (OXPHOS) and glutaminolysis to survive.

Targeting the OXPHOS pathway with a small molecule, IACS-010759, inhibited the proliferation of ibrutinib-resistant cells in vitro.

IACS-010759 also decreased tumor volume and improved survival in mouse models of ibrutinib-resistant MCL and double-hit B-cell lymphoma.

Now, IACS-10759 is being tested in phase 1 trials of lymphoma and solid tumors (NCT03291938) as well as acute myeloid leukemia (NCT02882321).

Liang Zhang, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted the preclinical research and described their findings in Science Translational Medicine.

The investigators sequenced samples from MCL patients with ibrutinib-sensitive and -resistant disease and found that “glutamine-fueled OXPHOS appears to be a prominent energy metabolism pathway in ibrutinib-resistant MCL cells.”

This finding prompted the team to test IACS-010759, an inhibitor of ETC complex I, in ibrutinib-resistant MCL. They theorized that the inhibitor would be effective because, during OXPHOS, electrons are transferred from electron donors to acceptors through the ETC in redox reactions that release energy to form ATP, and OXPHOS generates ATP to meet requirements for cell growth.

In experiments, IACS-010759 inhibited the proliferation of two ibrutinib-resistant MCL cell lines, Z-138 and Maver-1, in a dose-dependent manner.

The investigators also tested IACS-010759 in two mouse models of ibrutinib-resistant MCL. In both models, mice treated with IACS-010759 had a significant reduction in tumor volume, compared with controls. In one model, IACS-010759 extended survival by a median of 11 days.

Finally, the team tested IACS-010759 in a model of ibrutinib-resistant, double-hit (MYC and BCL-2) B-cell lymphoma with central nervous system involvement. Again, IACS-010759 significantly inhibited tumor growth. Compared to ibrutinib and vehicle control, IACS-010759 provided a median survival benefit of more than 20 days.

There were no toxicities associated with IACS-010759 treatment, according to the investigators.

This research was supported by the MD Anderson B Cell Lymphoma Moon Shot Project, Gary Rogers Foundation, Kinder Foundation, Cullen Foundation, Cancer Prevention Research Institute of Texas, and the National Institutes of Health. Most investigators reported having no competing interests, but two reported a patent (WO/2015/130790).

[email protected]

SOURCE: Zhang L et al. Sci Transl Med. 2019 May 8. doi: 10.1126/scitranslmed.aau1167.

Investigators have identified a mechanism of ibrutinib resistance in mantle cell lymphoma (MCL) and showed that a small molecule can overcome that resistance in vitro and in vivo.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The team found that ibrutinib-resistant MCL cells rely on oxidative phosphorylation (OXPHOS) and glutaminolysis to survive.

Targeting the OXPHOS pathway with a small molecule, IACS-010759, inhibited the proliferation of ibrutinib-resistant cells in vitro.

IACS-010759 also decreased tumor volume and improved survival in mouse models of ibrutinib-resistant MCL and double-hit B-cell lymphoma.

Now, IACS-10759 is being tested in phase 1 trials of lymphoma and solid tumors (NCT03291938) as well as acute myeloid leukemia (NCT02882321).

Liang Zhang, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues conducted the preclinical research and described their findings in Science Translational Medicine.

The investigators sequenced samples from MCL patients with ibrutinib-sensitive and -resistant disease and found that “glutamine-fueled OXPHOS appears to be a prominent energy metabolism pathway in ibrutinib-resistant MCL cells.”

This finding prompted the team to test IACS-010759, an inhibitor of ETC complex I, in ibrutinib-resistant MCL. They theorized that the inhibitor would be effective because, during OXPHOS, electrons are transferred from electron donors to acceptors through the ETC in redox reactions that release energy to form ATP, and OXPHOS generates ATP to meet requirements for cell growth.

In experiments, IACS-010759 inhibited the proliferation of two ibrutinib-resistant MCL cell lines, Z-138 and Maver-1, in a dose-dependent manner.

The investigators also tested IACS-010759 in two mouse models of ibrutinib-resistant MCL. In both models, mice treated with IACS-010759 had a significant reduction in tumor volume, compared with controls. In one model, IACS-010759 extended survival by a median of 11 days.

Finally, the team tested IACS-010759 in a model of ibrutinib-resistant, double-hit (MYC and BCL-2) B-cell lymphoma with central nervous system involvement. Again, IACS-010759 significantly inhibited tumor growth. Compared to ibrutinib and vehicle control, IACS-010759 provided a median survival benefit of more than 20 days.

There were no toxicities associated with IACS-010759 treatment, according to the investigators.

This research was supported by the MD Anderson B Cell Lymphoma Moon Shot Project, Gary Rogers Foundation, Kinder Foundation, Cullen Foundation, Cancer Prevention Research Institute of Texas, and the National Institutes of Health. Most investigators reported having no competing interests, but two reported a patent (WO/2015/130790).

[email protected]

SOURCE: Zhang L et al. Sci Transl Med. 2019 May 8. doi: 10.1126/scitranslmed.aau1167.

The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.

Mitchel L. Zoler/MDedge News

A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” Experts have estimated that, by early 2019, more than 500 cases of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) had been reported worldwide, roughly half of them in the United States.

In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.

During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).

Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.

[email protected]

The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.

Mitchel L. Zoler/MDedge News

A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” Experts have estimated that, by early 2019, more than 500 cases of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) had been reported worldwide, roughly half of them in the United States.

In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.

During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).

Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.

[email protected]

The Food and Drug Administration decided to continue to allow U.S. sales of textured breast implants, which have been identified as the cause of a rare but significant cancer, breast implant–associated anaplastic large cell lymphoma.

Mitchel L. Zoler/MDedge News

A statement the agency released on May 2 said “The FDA does not believe that, on the basis of available data and information, the device [textured implants] meets the banning standard set forth in the Federal Food and Drug Cosmetic Act.” Experts have estimated that, by early 2019, more than 500 cases of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) had been reported worldwide, roughly half of them in the United States.

In coming to this decision, following 2 days of public testimony and discussions by an advisory committee in late March, the FDA is bucking the path taken by regulatory bodies of the European Union as well as several other counties. The EU acted in December 2018 to produce the equivalent of a ban on sales of textured breast implants marketed by Allergan. Then in April 2019, the French drug and device regulatory agency expanded this ban to textured breast implants sold by five other companies.

During the FDA advisory committee meeting in March, one of the world’s experts on BIA-ALCL, Mark W. Clemens, MD, a plastic surgeon at MD Anderson Cancer Center in Houston, said that of about 500 case reports received by the FDA, not one had involved a confirmed and “pure” episode of BIA-ALCL linked with a smooth breast implant. A team of experts recently reached the same conclusion when reviewing the reported worldwide incidence of BIA-ALCL in a published review (Plast Reconstr Surg. 2019 March;143[3S]:30S-40S).

Despite these reports, the FDA said in its new statement that “While the majority of women who develop BIA-ALCL have had textured implants, there are known cases in women with smooth-surface breast implants, and many reports do not include the surface texture of the implant at the time of diagnosis.” The agency added that it is “focused on strengthening the evidence generated to help inform future regulatory action.” During the March advisory committee meeting, some members of the panel spoke against a marketing ban on textured implants for reasons such as the modest number of reported cases and because of the importance of having a textured implant option available.

[email protected]

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.

Chimeric antigen receptor (CAR) T-cell therapy bb2121, which targets B-cell maturation agent (BCMA), appears safe and effective for treating patients with refractory multiple myeloma, according to results of a phase 1 trial.

The objective response rate of 85% among 33 heavily pretreated patients suggests “promising efficacy,” reported lead author Noopur Raje, MD, of Massachusetts General Hospital Cancer Center in Boston and colleagues.

“Although comparisons among studies are complicated by differences in patient populations, CAR constructs, administered doses, and grading scales of toxic effects, the results observed with bb2121 indicate a favorable safety profile,” the investigators wrote in a study published in the New England Journal of Medicine.

The study initially involved 36 patients with refractory multiple myeloma who had received at least three lines of prior therapy, including an immunomodulatory agent and a proteasome inhibitor. Although leukapheresis and therapy manufacturing were successful in all patients, three patients were excluded from receiving the infusion because of disease progression.

The 33 remaining patients were lymphodepleted with fludarabine and cyclophosphamide. Bridging therapy was allowed during the manufacturing process but was stopped at least 2 weeks prior to infusion. In the dose-escalation phase of the study, b2121 was delivered as a single infusion at one of four dose levels: 50 × 10⁶, 150 × 10⁶, 450 × 10⁶, or 800 × 10⁶ CAR T cells. In the expansion phase, the treatment was given at either 150 x 10⁶ or 450 x 10⁶ CAR T cells. The primary endpoint was safety; the secondary endpoints were response rate and duration of response.

After a median follow-up of 11.3 months, most patients (85%) had responded to therapy, and almost half (45%) had achieved a complete response. Of the 15 complete responders, 6 relapsed. The median progression-free survival was 11.8 months; stated differently, two out of five patients (40%) had not experienced disease progression after 1 year. CAR T cells were detectable 1 month after infusion in 96% of patients; however, this value dropped to 86% at 3 months, 57% at 6 months, and 20% at 12 months. The investigators noted that CAR T-cell persistence was associated with treatment response.

All patients had adverse events. Most (85%) had grade 3 or higher hematologic toxicity, which the investigators considered to be the “expected toxic effects of lymphodepleting chemotherapy.” Although other adverse events occurred in the majority of patients, these were generally mild to moderate. Cytokine release syndrome occurred in 25 patients (76%), including two instances of grade 3 toxicity but none of grade 4 or higher. Fourteen patients (42%) developed neurologic toxicities: Most were grade 1 or 2, but one patient had a grade 4 toxicity that resolved after a month. Infections occurred at the same rate (42%), although, again, most were grade 1 or 2.

The study was funded by Bluebird Bio and Celgene. The investigators disclosed financial relationships with Bluebird and other drug companies.

SOURCE: Raje N et al. NEJM. 1 May 2019. doi: 10.1056/NEJMoa1817226.