Renal function eligibility in multiple myeloma CAR T and bispecific antibody clinical trials.

Abstract

e19528 Background: Chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs) have transformed the treatment of relapsed or refractory multiple myeloma (MM). Kidney impairment affects 20–50% of patients with MM and may limit access to these therapies, yet renal eligibility criteria in CAR-T and BsAb trials remain inconsistently defined. We systematically reviewed renal eligibility criteria in MM CAR-T and BsAb clinical trials. Methods: We systematically reviewed 202 MM CAR-T and BsAb clinical trials registered on ClinicalTrials.gov. Renal eligibility criteria were extracted when available and defined using either creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), depending on trial reporting. Thresholds were categorized as permissive (0–39), moderate (40–59), or restrictive (≥60). Results: Of 202 trials, 28% (n = 57) reported a renal eligibility criterion. Among these, the most common threshold was CrCl or eGFR ≥30 mL/min, used in 51% (n = 29) of studies. More restrictive thresholds were frequently applied, with 23% (n = 13) requiring CrCl or eGFR ≥40–45 mL/min and 5% (n = 3) requiring ≥60 mL/min. Only 5% (n = 3) of trials permitted enrollment of patients with advanced renal impairment (CrCl or eGFR ≤20 mL/min). Fourteen percent (n = 8) of studies used nonspecific language such as “adequate renal function” without defining a numeric cutoff, and 2% (n = 1) explicitly excluded dialysis patients without specifying a renal function threshold. Renal thresholds did not differ significantly between CAR-T and BsAb trials. Most trials reporting renal criteria were conducted in the United States (67%), followed by international multicenter studies (19%), Europe (7%), and China (4%). Academic-sponsored studies accounted for 74% (n = 42/57) of trials reporting renal thresholds, compared with 26% industry-sponsored trials. Conclusions: Despite FDA labeling indicating no clinically meaningful pharmacokinetic differences for CAR-T cells and BsAbs in patients with mild to moderate renal impairment, over one-quarter of trials applied unnecessarily restrictive renal eligibility criteria. Exclusion of patients with CrCl 30-59 mL/min may not be pharmacokinetically justified and contributes to limited access and evidence gaps. Standardized, evidence-based renal eligibility criteria are needed to improve trial inclusivity and equity in MM.