Efficacy and Safety of CAR-T Cell Therapy and Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma with Renal Impairment: A Propensity Score-Matched Analysis

T-cell-redirecting immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAbs), have transformed the treatment of relapsed/refractory multiple myeloma (RRMM). However, pivotal registration trials routinely excluded patients with significant renal impairment (RI), creating a critical evidence gap in a population where kidney disease affects 20-50% of patients at diagnosis. Direct comparisons of outcomes across the estimated glomerular filtration rate (eGFR) spectrum for both modalities are lacking.

We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, a federated electronic health record research platform. Adult patients with RRMM treated with CAR-T therapy (idecabtagene vicleucel or ciltacabtagene autoleucel) or BsAbs (teclistamab, elranatamab, or talquetamab) were stratified by baseline renal function: severe RI (eGFR <30 mL/min/1.73 m²), moderate RI (eGFR 30-60 mL/min/1.73 m²), and preserved renal function (eGFR >60 mL/min/1.73 m²). Propensity score matching (PSM) (1:1), adjusted for key clinical and demographic covariates, was performed for each comparison within each therapy type. Long-term outcomes (all-cause mortality and time to next treatment [TTNT]) were assessed at 1, 2, and 3 years. Overall survival (OS) was additionally evaluated using Kaplan-Meier analysis. Short-term safety outcomes were assessed at 1, 3, and 6 months.

A total of 2716 CAR-T and 3376 BsAb recipients were identified. After matching, 281 pairs (severe RI vs. preserved) and 878 pairs (moderate RI vs. preserved) were analyzed in the CAR-T cohort; 645 and 1158 pairs, respectively, were analyzed in the BsAb cohort. Neither severe nor moderate RI was significantly associated with increased mortality or shorter TTNT after either CAR-T or BsAb therapy. However, patients with RI experienced significantly higher rates of anemia, thrombocytopenia, and acute kidney injury (AKI) across both modalities. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and neutropenia rates were comparable across renal strata. In the BsAb cohort, infections were transiently elevated at 1 month in the severe RI group (RR 1.29; 95% CI 1.06-1.58; p = 0.011) but equilibrated by 3 months.

In this retrospective analysis, renal impairment was not associated with inferior survival outcomes following CAR-T therapy or BsAb treatment in RRMM, suggesting that RI alone should not preclude the use of these agents. However, RI conferred increased hematologic toxicity and AKI risk, warranting enhanced supportive care and monitoring. These findings support broadening access to T-cell-redirecting immunotherapies for patients with RI with appropriate surveillance, though prospective validation is needed.