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

Approval Alert | <b>Liso-Cel for Relapsed/Refractory LBCL in Second Line</b>

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.

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.1 CancerNetwork® 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 phase 3 TRANSFORM trial (NCT03575351) 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.2


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.


  1. 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.
  2. 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