Dr Sidana on CAR T-cell Therapy in Patients With R/R Myeloma and Renal Impairment

Surbhi Sidana, MD, assistant professor, medicine, Department of Medicine, Division of Blood and Marrow Transplantation & Cellular Therapy, leader, Myeloma Cellular Immunotherapy program, Stanford University School of Medicine, discusses the unmet needs for patients with relapsed/refractory multiple myeloma who could be candidates for CAR T-cell therapy but have impaired renal function, and how clinical trials for these therapies have excluded this subset of patients.

BCMA-directed CAR T-cell therapies represent a promising treatment option for patients with relapsed/refractory multiple myeloma, and the FDA has approved 2 products for patients who have received at least 4 lines of prior therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody: idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti), Sidana begins. Ide-cel was approved in March 2021 based on results from the phase 2 KarMMa trial (NCT03361748), and cilta-cel was approved in February 2022 based on findings from the phase 1b/2 CARTITUDE-1 trial (NCT03548207). 

However, in both trials, investigators excluded any patients with renal impairment, Sidana explains. Renal impairment affects a significant proportion of patients with multiple myeloma, including up to one-fourth of patients at diagnosis and an even higher proportion of patients at the time of relapse, Sidana notes.

In a retrospective analysis presented at the 2023 Transplantation & Cellular Therapy Meetings, investigators looked at real-world outcomes for patients treated with ide-cel. Findings showed that regarding safety, the rates and severity of cytokine release syndrome and neurotoxicity were similar between the patients with renal impairment and those with normal renal function. Additionally, the overall response rates and median progression-free survival were comparable between the 2 groups.

Because clinical trials are often highly selective when enrolling patients, patients with reduced renal function are sometimes left out, Sidana adds. In the studies of ide-cel and cilta-cel, this may have stemmed from a lack of a full toxicity and safety profile for the CAR T-cell therapies, which are still new to the myeloma space, Sidana says. Given the findings of the real-world retrospective study, once it established that there is a product that works, investigators should be inclusive of other cohorts of patients that better represent the real-world population, such as those with multiple myeloma who have renal dysfunction, Sidana concludes.