David S. Siegel

Multiple myeloma (MM) patients with end-stage renal disease (ESRD) requiring hemodialysis (HD), who are disproportionately Black, have been excluded from all pivotal trials of BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, leaving a critical evidence gap in a population. We conducted a multicenter retrospective analysis of all MM patients who received CAR-T therapy while on HD at two U.S. centers between June 2021 and December 2025. Of 284 CAR-T recipients, 8 (2.8%) were HD-dependent. Median age was 63 years; 62.5% were female and 75% were Black; patients had received a median of 6 prior lines. Five received ciltacabtagene autoleucel and three received idecabtagene vicleucel; lymphodepletion was bendamustine (n = 4) or dose-reduced fludarabine/cyclophosphamide (n = 4). Cytokine release syndrome occurred in 37.5% (all Grade 1), with no grade ≥ 3 events—substantially lower than pivotal trials (76–95%). All 7 evaluable patients achieved neutrophil recovery by Day 30. One patient with prolonged pre-existing cytopenia pre-CAR-T therapy developed ICAN grade 4 and died from fungal pneumonia. Median progression-free survival was 17.5 months and median overall survival was not reached. Treatment-related mortality was 12.5%. CAR-T therapy is feasible, relatively safe, and effective in carefully selected HD-dependent MM patients, supporting expanded eligibility with appropriate dose modification.

Patient disposition flow chart

Violin plot showing sBCMA (ng/mL) at progressive disease visit or closest visit within a 30-day window (n = 31)

Functional persistence of CAR T cells may not be sufficient for durable response, as determined by VCN persistence and sBCMA levels

Bb007 leads to enrichment of memory phenotype, which results in improved persistence in in vivo models.

Representativeness of Study Participants

Chimeric antigen receptor (CAR) T-cell therapy enriched for a memory-like phenotype may persist and function longer than a nonenriched product, thereby improving duration of response (DOR). We conducted a phase I study with bb21217 (NCT03274219), an anti–B-cell maturation antigen CAR T-cell therapy manufactured in the presence of the phosphoinositide 3-kinase inhibitor bb007 to enrich for T cells with a memory-like phenotype, in patients with relapsed/refractory multiple myeloma (N = 72). No new safety concerns were raised with bb21217 therapy (three cases each of grade ≥3 cytokine release syndrome and grade ≥3 neurotoxicity were observed). The objective response rate was 69.4% and the median DOR was 23.8 (95% confidence interval, 16.8–34.8) months. Analysis of the drug product established an association between early memory phenotype and robust expansion and depth of response. Examination of baseline characteristics indicated that tumor burden and prior therapies influenced DOR. The data indicate that generation of CAR T cells early in a disease course when tumor burden is lower and source material exhibits a more naïve phenotype may maximize the clinical benefit potential of the drug product.