A Real-World Analysis of the Safety and Efficacy of BCMA-Directed CAR T-Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma and Baseline Renal Impairment

Introduction: Novel treatments targeting B-cell maturation antigen (BCMA), such as ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel), have shown promising results in treating relapsed or refractory multiple myeloma (RRMM). Despite significant clinical improvements in patients, there is limited real-world evidence on outcomes and toxicities in patients with baseline renal impairment (RI) receiving BCMA chimeric antigen receptor T-cell therapy (CART).

Methods: This multicenter, retrospective study includedRRMM patients who received either cilta-cel or ide-cel at multiple U.S. academic institutions in collaboration with US Myeloma Innovations Research Collaborative (USMIRC). Renal impairment was defined as a creatinine clearance <45 mL/min. Responses to therapy were evaluated using the International Myeloma Working Group (IMWG) criteria. Adverse events were graded based on the CTCAE v5.0 criteria. Using R Core Team (2024) software, a descriptive analysis was performed. Continuous variables were summarized and reported the mean (min, max) and median (IQR). Dichotomized factors were summarized by total numbers and frequency. Fisher's exact test was used to analyze contingency tables, and Wilcoxon rank-sum test to compare two independent samples. Kaplan-Meier methods were used for progression-free (PFS) and overall survival (OS) calculations.

Results: BetweenMay 2021 and April 2024, 223 patients who received ide-cel or cilta-cel were evaluated. Twenty-five (11%) patients had baseline RI; none of the patients had end-stage renal disease or required hemodialysis. Median age was 64 years (range: 34-84 years), 56% were male, 17% were Black and 0.9% Hispanic. Median prior lines of therapy were 6 (3-13) and 83% underwent at least one autologous stem cell transplantation. Patients with RI were more likely to have Revised International Staging System stage III disease, 53% vs 26% (p=0.03) in the control group. Similar characteristics were observed between subgroups which included poor prognostic features, such as high-risk cytogenetics (40% vs 34.1%, p=0.3-0.6) and extramedullary disease (32% vs 38%, p=0.6), and previous exposure to anti-BCMA therapies (12% vs 13%, p>0.9). Of the patients with RI, 21 (84%) received ide-cel and 4 (16%) cilta-cel.

The incidence of grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) was higher in patients with baseline RI (12% vs 2%, p=0.023). Infection was more prevalent in the baseline RI group (44% vs 20%, p=0.008). There was a strong trend towards overall frequency of cytokine release syndrome (CRS) with baseline RI (96% vs 80%, p=0.055); grade ≥3 CRS was rare (0% vs 1%, p=0.065). There were no significant differences in cytopenias reported at 30-days [(ANC: 1.47 vs 1.68, p=0.6) (Hgb: 9.47 vs 10.56, p=0.12) (Plt 70 vs 75, p=0.12)], 60-days [(ANC: 1.89 vs 2.33, p=0.6) (Hgb: 9.77 vs 11.91, p=0.1) (Plt 110 vs 110, p>0.9)], and 90-days [(ANC: 2.80 vs 2.60, p=0.5) (Hgb 10.5 vs 10.9), p=0.2) (Plt: 122 vs 120, p=0.9). No significant difference was found in the duration of hospitalization [10 days (range: 8-15) vs 10 days (7-15, p>0.9)]. Similar response rates were seen at 1-month (p=0.088), 3-months (p>0.9), and 6-months (p=0.8). At 30-days, 17 (74%) vs 83 (47.9%, p=0.088) patients achieved a VGPR or better. With median follow-up range (IQR) of 27.9 months (11; NA), progression-free survival (PFS) was 21.9 months vs 15 months (p=0.3188). Overall survival (OS) was 27.9 months vs Not Reached (p=0.8715).

Conclusions: RRMM with baseline RI exhibited increased rates of ICANS and infection, yet PFS, OS, and other toxicity profiles showed no significant differences between the groups. This real-world, multicenter experience underscores the comparable efficacy and safety of BCMA CART in RRMM patients with baseline RI. However, closer monitoring may be warranted for patients with baseline RI as they may experience more pronounced ICANS and infection rates.

Ahmed:Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Legend Biotech: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Khan:BMS: Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Research Funding, Speakers Bureau. Paul:Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; AbbVie Inc: Membership on an entity's Board of Directors or advisory committees. Strouse:Seagen: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Bristol Meyer Squibb: Research Funding; Poseida: Research Funding. Davis:Janssen Biotech: Speakers Bureau. Mahmoudjafari:Janssen: Consultancy; Sanofi: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding. McGuirk:Caribou bio: Consultancy; Legend biotech: Consultancy; Autolus: Consultancy; Allo Vir: Consultancy; Envision: Consultancy; Sana technologies: Consultancy; CRISPR therapeutics: Consultancy; NEKTAR therapeutics: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy.