The FDA has approved lisocabtagene maraleucel (liso-cel; Breyanzi) as treatment for relapsed/refractory large B-cell lymphoma (LBCL) following 1 prior line of therapy, according to Bristol Myers Squibb.

The newly approved indication extends to patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from indolent lymphoma; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma. Disease could be refractory to or relapsing within 12 months of frontline chemoimmunotherapy or relapsed/refractory to chemoimmunotherapy and ineligible for hematopoietic stem cell transplant.

“Breyanzi represents a remarkable advance over a nearly 30-year standard of care, providing significantly improved efficacy with a well-established safety profile,” Manali Kamdar, MD, associate professor and clinical director of Lymphoma Services, Division of Hematology, Hematologic Malignancies and Stem Cell Transplantation at the University of Colorado Cancer Center, said in a press release. “This important milestone reinforces the benefit of offering a CAR T-cell therapy option to patients earlier in their treatment journey and it’s critical that we begin the work to implement this therapy into standard practice as a second-line treatment in order to help improve outcomes for more patients.”

 in which patients treated with liso-cel had statistically significant improvement in event-free survival (EFS) compared with the standard of care (SOC). The median EFS in the liso-cel arm (n = 92) was 10.1 months (95% CI, 6.1–not reached [NR]) vs 2.3 months (95% CI, 2.2-4.3) in the SOC arm (n = 92; HR, 0.349; 95% CI, 0.229-0.530; 

 <.0001). At 6 months, the EFS rates were 63.3% (95% CI, 52.0%-74.7%) and 33.4% (95% CI, 23.0%-43.8%), and at 12-months were 44.5% (95% CI, 29.4%-59.6%) and 23.7% (95% CI, 13.4%-34.1%) in the liso-cel and SOC arms, respectively.

The objective response rate in the liso-cel arm was 86% (95% CI, 77.0%-92.3%) vs 48% (95% CI, 37.3%-58.5%) in the SOC arm. Those treated with liso-cel had a complete response rate of 66% (95% CI, 55.7%-75.8%; 

 <.0001) vs 39% (95% CI, 13.4%-34.1%) in the SOC arm (

The median progression-free survival (PFS) was 14.8 months (95% CI, 6.6-NR) in the liso-cel arm compared with 5.7 months (95% CI, 3.9-9.4) in the SOC arm (HR, 0.406; 95% CI, 0.250-0.659; 

Grade 3 or higher treatment-emergent adverse effects (TEAEs) in the liso-cel arm included neutropenia (80%), anemia (49%), thrombocytopenia (49%), and lymphopenia (25%). In 48% of patients in both arms, serious TEAEs were identified. Any-grade cytokine release syndrome was observed in 49 patients in the liso-cel arm, with a median time to onset of 5 days and a median time to resolution of 4 days.

Of 232 patients who were screened, 184 received leukapheresis and were randomized 1:1. At the time of data reporting, 78 patients were continuing treatment in the liso-cel arm vs 32 in the SOC. Fifty patients crossed over from the SOC arm to receive liso-cel, with 46 ultimately receiving CAR T-cell therapy as their third-line treatment.

At data cut-off, the median follow-up for the liso-cel and SOC cohorts was 6.2 months. Patients included in the analysis underwent leukapheresis and then randomization, with the liso-cel arm receiving 100 x 10

 CAR T cells and the SOC arm having 3 cycles of salvage therapy then high-dose chemotherapy plus autologous stem cell transplantation.

U.S. FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. Accessed June 25, 2022. https://bit.ly/3bwiw1D

Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, versus standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B lymphoma (LBCL): results from the randomized phase 3 transform study. 

. 2021;138(1):91. doi:10.1182/blood-2021-147913

Articles

Based on results from the phase 3 TRANSFORM trial, the FDA has approved lisocabtagene maraleucel for the second-line treatment of relapsed/refractory large B-cell lymphoma.

FDA Approves Liso-Cel for Second-Line Relapsed/Refractory LBCL

Liso-Cel for Relapsed/Refractory LBCL in Second Line

Lisocabtagene maraleucel (liso-cel; Breyanzi) was recently approved for the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma not otherwise specified; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma.

 spoke with Catherine S. Diefenbach, MD, director of both Hematology and Translational Research and the Clinical Lymphoma Program of Perlmutter Cancer Center at NYU Langone Health, about data from the 

 that led to the approval and how the indication for this and other similar therapies may be expanded in the future with better understand regarding how to tailor the therapy.

There are a couple of steps that are going to be important. One is to get a better idea of who benefits so we can tailor this therapy to the patients who are going to benefit the most. We need to get better at understanding the mechanisms of relapse and nonresponse to CAR T-cell therapy so that we [avoid subjecting] patients to this toxic therapy who are unlikely to benefit and/or design a next-generation CAR T-cell treatment that is going to allow more patients to have a durable response and be cured than what is currently approved. We need to get better at managing the toxicity of CAR T cells because this is still a fairly toxic therapy, and design next-generation CAR T cells that are less toxic. We need to get better about improving access so more patients can have access to CAR T cells. There are still many issues around insurance and payments for commercial CAR T cells. From a drug development, a clinical, and a public health standpoint, there’s still much work that we can do to optimize this therapy.

This is an exciting time in lymphoma. We have a new therapy that was approved initially in the third line that’s now moving to the second line and other exciting therapies that are nearing approval. We have more ways than ever to cure patients with lymphoma or extend the lives of people with incurable lymphoma. The challenge going forward is going to understand who benefits from which therapy and understand how to optimize response for all patients with these exciting therapies that we now have. This is an absolutely wonderful and transformative development.

U.S. FDA approves Bristol Myers Squibb’s CAR T cell therapy Breyanzi for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. June 24, 2022. Accessed June 28, 2022. https://bit.ly/3bwiw1D

Videos

Catherine S. Diefenbach, MD, spoke about refining understanding of CAR T-cell therapies after the approval of lisocabtagene maraleucel for patients with relapsed/refractory large B-cell lymphoma. 

Catherine S. Diefenbach, MD, Talks Future of CAR T-cell Therapy Following Liso-Cel Approval in Second-Line LBCL

 spoke with Catherine S. Diefenbach, MD, director of both Hematology and Translational Research and the Clinical Lymphoma Program of Perlmutter Cancer Center at NYU Langone Health, about the 

recent approval of lisocabtagene maraleucel (liso-cel; Breyanzi)

 for the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL).

 The approval includes patients who have diffuse large B-cell lymphoma not otherwise specified, including DLBCL arising from indolent lymphoma; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma may receive this treatment as well. Results from the 

 supported the approval, with a median event-free survival of 10.1 months (95% CI, 6.1-not reached) with liso-cel vs 2.3 months (95% CI, 2.2-4.3) with standard of care in the indicated patient population.

Patients who do not have chemotherapy-sensitive disease historically have extremely poor outcomes to second- and third-line chemotherapy, which is just more of the same. If you don’t respond to first-line chemotherapy, your chances of responding to each subsequent line of chemotherapy get smaller and smaller, and your chances of cure with an autologous stem cell transplant—which is a way to deliver higher doses of chemotherapy, there’s nothing immunologic about autologous transplant—wasn’t likely to cure you if you didn’t have sensitive disease to begin with. These patients who have primary refractory DLBCL are generally dying within a year of their relapse. This is a huge unmet need for which CAR T cells are, not curing all these patients, curing some of these patients. That is addressing a tremendous unmet medical need.

Catherine S. Diefenbach, MD, spoke about the approval of lisocabtagene maraleucel for patients with relapsed/refractory large B-cell lymphoma who do not have chemotherapy-sensitive disease. 

Catherine S. Diefenbach, MD, Discusses Gaps Filled by Approval of Liso-Cel in Second-Line Relapsed/Refractory LBCL

Catherine S. Diefenbach, MD, director of both Hematology and Translational Research and the Clinical Lymphoma Program of Perlmutter Cancer Center at NYU Langone Health, spoke with CancerNetwork

 (liso-cel; Breyanzi) for the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL).

Specifically, the approval covered patients with diffuse large B-cell lymphoma that is not otherwise specified, including DLBCL arising from indolent lymphoma; high-grade B-cell lymphoma; primary mediastinal LBCL; and grade 3B follicular lymphoma. The approval is based on results from the 

, which showed a median event-free survival of 10.1 months (95% CI, 6.1-not reached) with liso-cel vs 2.3 months (95% CI, 2.2-4.3) with standard of care in the indicated patient population.

What is transformative about the approval of liso-cel is it’s for patients who did not respond to initial chemotherapy or were considered to have primary refractory disease because they relapsed within 6 months of their initial chemotherapy. Their outcomes, even with autologous stem cell transplantation, were exceedingly poor. To be cured with autologous stem cell transplant, data show that patients who are in a complete response, that is all of their tumor after second-line therapy is gone or nearly gone, have the best outcome. Even for these patients, the cure rate is only 50%. We know that patients who do not have a chemotherapy-sensitive disease who can’t get into remission with second-line or third-line therapy have almost no chance of being cured by an autologous stem cell transplant.

CAR T-cell therapy is transformative because patients can be cured, even with chemotherapy-refractory disease. For patients in the TRANSFORM trial who had primary refractory disease who didn’t respond to their first-line chemotherapy or who relapsed within a short time period—within 12 months of first-line therapy, even with a crossover—there was a trend toward overall survival that favored CAR T-cell therapy, which is really exciting. It is certainly an improvement in progression free survival. This really gives these patients a curative option, particularly for the highest risk patients that they didn’t have.

Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, versus standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B lymphoma (LBCL): results from the randomized phase 3 transform study. Blood. 2021;138(1):91. doi:10.1182/blood-2021-147913

Catherine S. Diefenbach, MD, spoke about the approval of lisocabtagene maraleucel for the treatment of relapsed/refractory large B-cell lymphoma following 1 prior therapy. 