Dr Callander on Early CAR T-cell Therapy Referrals in Multiple Myeloma

Natalie S. Callander, MD, associate professor, Division of Hematology, Medical Oncology, and Palliative Care, Department of Medicine, University of Wisconsin School of Medicine and Public Health; director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, discusses the potential benefits of referring patients with multiple myeloma to CAR T-cell therapy earlier in their disease course.

The 2 CAR T-cell therapies currently approved for patients with multiple myeloma are idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti). Ide-cel was approved for patients with multiple myeloma in 2021 based on findings from the phase 2 KarMMa trial (NCT03361748), in which ide-cel infusion led to an overall response rate (ORR) of 72%. Cilta-cel was approved for patients with relapsed/refractory multiple myeloma in February 2022 based on data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207), in which patients who received this therapy achieved an ORR of 97%.

However, based on findings from the phase 3 CARTITUDE-4 (NCT04181827) and KarMMa-3 (NCT03651128) trials, the FDA may revise the labeling for cilta-cel and ide-cel in multiple myeloma, Callander says. Currently, both CAR T-cell products are approved for patients who have already received at least 4 prior lines of therapy, although heavily pretreated patients are often no longer fit for CAR T-cell therapy, or do not derive the most benefit from this treatment, Callander explains.

The CARTITUDE-4 trial met its primary end point of progression-free survival (PFS) improvement with cilta-cel vs pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in patients with multiple myeloma who were relapsed/refractory to 1 to 3 prior lines of therapy. Additionally, in the KarMMa-3 trial, patients with multiple myeloma who were relapsed/refractory to 2 to 4 prior lines of therapy had a median PFS of 13.3 months with ide-cel vs 4.4 months with standard of care.

Data from CARTITUDE-4 and KarMMA-3 support the early referral of patients to CAR T-cell therapy so they are fit to receive this treatment and have the potential for a long period off therapy before requiring further treatment, Callander emphasizes. The combination of early discussions about CAR T-cell therapy with patients and potential changes to the FDA labeling for these products may positively alter the multiple myeloma treatment landscape, Callander concludes.