Dr. Cohen on the Use of CAR T-cell Therapy in Earlier Lines of Multiple Myeloma Treatment

Adam D. Cohen, MD, director, Myeloma Immunotherapy, associate professor in medicine, hematology/oncology, Abramson Cancer Center, University of Pennsylvania, discusses a presentation given at the Baptist Health South Florida Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies on the current landscape of treatment options in multiple myeloma, and elaborates on attempts to utilize these options in earlier lines of therapy. 

Two CAR T-cell therapies are currently FDA approved for the treatment of patients with multiple myeloma, including idecabtagene vicleucel (ide-cel; Abecma) for patients with relapsed/refractory disease who have progressed on 4 or more previous lines of therapy, Cohen begins. This includes a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This approval was based on findings from the phase 2 KarMMa trial (NCT03361748).

Following the FDA approval of ide-cel for this patient population, the FDA then approved treatment withciltacabtagene autoleucel (cilta-cel; Carvykti) for patients with relapsed or refractory disease after 4 or more prior lines of therapy. This approval was based on data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), which showed that patients receiving cilta-cel achieved an objective response rate (ORR) of 98% and a stringent complete response rate of 78%. 

These studies show that patients who have previously undergone BCMA-directed therapy can still respond to subsequent CAR T-cell therapies, Cohen says. However, the durability of responses may be decreased in later-line settings, he notes. Moreover,, the use of CAR T-cell therapies in earlier lines of treatment is of great interest in the field, Cohen explains. 

For example, the phase 3 KarMMa-3 trial (NCT03651128) attempted to investigate the use of ide-cel vs standard-of-care regimens in patients with triple-class exposed relapsed/refractory multiple myeloma, Cohen details, adding that this patient population recieved fewer prior lines of therapy than patients in previous studies. On this study, ide-cel is being compared with investigator's choice of therapy, which includes daratumumab (Darzalex), pomalidomide (Pomalyst), dexamethasone, bortezomib (Velcade) and ixazomib (Revlimid). The trial's primary end point was progression-free survival (PFS).

Based on data from KarMMa-3 that were published in the New England Journal of Medicine, patientsreceiving ide-cel were shown to have a significantly improved PFS vs its comparator arms, Cohen says. This trial demonstrated the efficacy and utility of ide-cel and may support future attempts to expand ide-cel's approval to less heavily pretreated populations, Cohen concludes.

Editor’s Note: Dr. Cohen reports serving as a consultant or in an advisory role for Celgene, BMS, Takeda, Janssen, Seattle Genetics, AstraZeneca, Genentech/Roche, Oncopeptides, GlaxoSmithKline, Arcellx, Ichnos; he received research funding from Novartis, GlaxoSmithKline; he has intellectual property licensed by institution to Novarti.