# BCMA-Directed CAR T-Cell Therapy in Patients with Relapsed/Refractory Multiple Myeloma and Renal Impairment

## TL;DR

This study shows that BCMA-directed CAR T-cell therapy is effective for multiple myeloma patients with kidney issues, though it carries higher risks of side effects like neurotoxicity and infections.

## Contribution

The study provides evidence that BCMA CAR-T therapy is effective in multiple myeloma patients with renal impairment, a group often excluded from clinical trials.

## Key findings

- Response rates were similar between patients with renal impairment and normal renal function.
- Patients with renal impairment had higher rates of neurotoxicity and infections.
- Progression-free and overall survival were comparable between the two groups.

## Abstract

Multiple myeloma (MM) is currently an incurable disease. To advance the treatment options for MM, several clinical trials are testing novel therapies; however, individuals with organ dysfunction, such as renal impairment, often are not enrolled due to strict inclusion criteria. In this study, we evaluated the safety and efficacy of B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell therapy (CAR-T) in the treatment of aggressive, relapsed, and refractory MM. We found that BCMA CAR-T has comparable efficacy in patients with renal impairment, although there are potential increased rates of adverse effects of the treatment including neurotoxicity and infections.

The pivotal clinical trials, CARTITUDE-1 and KarMMa-3, showed promising response rates in relapsed and refractory multiple myeloma (RRMM) with use of BCMA-directed CAR T-cell therapy; however, a major challenge is determining suitability in patients who do not meet trial inclusion criteria due to suboptimal organ function. In this multicenter retrospective study, we evaluated the safety and efficacy of BCMA CAR-T therapy in patients with RRMM and renal impairment (RI), defined as creatinine clearance (CrCL) of less than 45 mL/min. We evaluated 223 patients treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) between May 2021 and April 2024. Outcomes were compared between baseline RI (11.2%) and normal renal function (nRF) cohorts. Response rates were similar at 1 month (p = 0.09), 3 months (p > 0.9), and 6 months (p = 0.8). Progression-free survival (PFS) was 21.9 months in the RI group compared to 15 months in the nRF group (p = 0.32), while overall survival (OS) was 27.9 months for patients with nRF versus not reached for patients with RI (p = 0.87). Patients with RI had higher rates of immune effector cell-associated neurotoxicity syndrome (ICANS) (60% vs. 19%, p = 0.04) and infections (44% vs. 20%, p = 0.008). We found that BCMA CAR-T demonstrated comparable efficacy in RRMM patients with baseline RI, although these patients exhibited increased rates of neurotoxicity and infections.