Infectious Complications during Treatment with Commercial CAR T-Cell Therapy and Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma

Introduction: Infections cause significant morbidity among relapsed refractory multiple myeloma (RRMM) patients receiving chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs). Real-world infection data in patients receiving commercial BsAbs and CAR T-cell therapy as standard of care are lacking and necessary to understand risk factors for serious infections, guiding treatment choices, and management strategies.

Methods: This isa retrospective single-center study of infectious complications in RRMM patients during treatment with commercial CAR T-cell therapy, idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel), and BsAbs, including teclistamab, elranatamab, or talquetamab between 8/1/2023-6/1/2024. Infections were graded in accordance with Common Terminology Criteria for Adverse Events v5.0. Patients received antiviral and PJP prophylaxis per standardized institutional guidelines. The primary endpoint was rate of total and serious infections (grade ≥3). Secondary objectives included time to first infection and impact of baseline characteristics on infectious complications.

Results: A total of 119 patients (55% Female, 68% Caucasian, 19% Black) were included; 69 treated with BsAbs and 50 treated with CAR T-cells. The BsAb group was older (median age 70 vs 66; p=0.041), had more prior lines of therapy (median 6 vs 5; p=0.01), a greater proportion of high-risk cytogenetics (61% vs 20%; p<0.001), a greater proportion of extramedullary disease (43% vs 12%; p<0.001), a lower baseline median hemoglobin (8.8 vs 11.40 g/dL; p<0.001), and a lower baseline median IgG (432 vs 592 mg/dL; p=0.028). Baseline ECOG, neutrophils, lymphocytes, and platelets were similar. Median follow-up was 3.7m (0.13-11.3m) for BsAbs and 5.3m (1.15-10.25m) for CAR T-cells.

Overall, 173 infections were reported with 106 amongst 46 (67%) BsAb patients and 67 amongst 26 (52%) CAR T-cell patients. Upper respiratory tract infections were the most common infections amongst both BsAb and CAR T-cell patients (39% and 49%). The BsAb group had a higher proportion of bacterial infections compared to the CAR T-cell group (49% vs 26%), but a lower proportion of viral infections, (47% vs 60%). Fungal infections were uncommon with 4 reported in the BsAb group and 1 in the CAR T-cell group. Recurrent infections (≥2) were more common in the BsAb group (43% vs 28%).

A total of 55 serious infections, not including grade 5, were reported with 43 amongst 28 (41%) BsAb patients and 12 amongst 7 (14%) CAR T-cell patients. Grade 5 infections occurred in 5 BsAb patients and 1 CAR T-cell patient. Recurrent serious infections were more common in the BsAb group (20% vs 6%). In a multivariable analysis, CAR T-cell therapy was associated with a lower rate of serious infections (incidence rate ratio [IRR]: 0.25, 95% CI 0.12-0.51;p<0.001). Male sex (IRR: 3.02 95% CI: 1.70-5.57; p<0.001) was also associated with an increased rate of serious infections.

The estimated cumulative incidence of first infection was higher in the BsAb group at day 30 (42% vs 24%) and day 90 (57% vs 40%). Estimated cumulative incidence of first serious infection was also higher in the BsAb group at day 30 (23% vs 6%) and day 90 (31% vs 10%). In a multivariable analysis, CAR T-cell therapy was associated with a longer time to first serious infection (HR 0.33, 95% CI 0.13-0.87; p=0.019). Male sex was associated with a shorter time to first serious infection (HR 2.95, 95% CI 1.40-6.21; p=0.003).

There were no differences in infection incidence or time to first infection between ide-cel or cilta-cel nor were there differences seen between BCMA-targeted BsAbs, teclistamab and elranatamab, and GPRC5D-targeted talquetamab. Baseline thrombocytopenia (<100k), neutropenia (ANC<1000), lymphopenia (ALC<500), and hypogammaglobulinemia (IgG<400) were not associated with infection incidence or time to first infection.

Conclusion: Infections were common amongst RRMM patients treated with commercial BsAbs and CAR T-cell therapy. In a real-world setting with standardized antimicrobial prophylaxis, BsAbs were associated with a higher incidence of total, serious, and recurrent infections which occurred earlier during treatment. The BsAb group had more high-risk features and more severe anemia at baseline likely contributing to infection incidence. Longer follow-up with more patients and extended analysis will be presented at the meeting.

Shekarkhand:Roche-Genentech: Consultancy. Lesokhin:Memorial Sloan Kettering Cancer Center: Current Employment; Arcellx: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Serametrix, Inc.: Patents & Royalties; F. Hoffmann-La Roche Ltd, Janssen, SVB Leerink: Consultancy, Honoraria. Korde:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen, Janssen, Epizyme, and AbbVie: Research Funding; Remedy Health 8/2022: Other: part of (Patient Power); CCO, OncLive, and Intellisphere: Consultancy. Tan:Takeda: Research Funding; Sanofi: Honoraria; Janssen: Honoraria, Research Funding. Hashmi:Janssen: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy. Hassoun:Janssen, Takeda: Research Funding. Shah:Janssen: Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Sanofi: Honoraria. Hultcrantz:Abbvie, GlaxoSmithKline, SpringWorks Therapeutics, Daiichi Sankyo, Cosette Pharmaceuticals: Research Funding; Curio Science LLC, Intellisphere LLC, Janssen, Bristol Myers Squibb, and GlaxoSmithKline: Consultancy, Honoraria. Landau:Abbvie, Immix Biopharma, Legend Biotech, Alexion, Prothena: Consultancy; Janssen, Alexion, Protego, Prothena: Research Funding. Scordo:Angiocrine Biosciences, Inc.: Research Funding; Sanofi: Research Funding; Amgen: Research Funding; Medscape: Honoraria; Miltenyi Biotec: Consultancy; IDEOlogy: Honoraria; Kite - A Gilead Company: Consultancy; MJH Life Sciences (Cancer Network): Honoraria; Omeros Corporation: Consultancy, Research Funding. Shah:Janssen, Amgen, Beyond Spring, BMS, GPCR, DSMB with ArcellX.: Research Funding. Usmani:Bristol-Myers Squibb - Celgene: Consultancy, Research Funding; Array Biopharma: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb - Celgene:: Consultancy, Research Funding; SeaGen: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Oncopeptides: Consultancy; GSK: Consultancy, Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; EdoPharma: Consultancy; Sanofi: Consultancy, Research Funding; Pfizer: Consultancy; Genentech: Consultancy; Gilead: Research Funding; SkylineDX: Consultancy, Research Funding; SecuraBio: Consultancy; Abbvie: Consultancy, Research Funding; Gracell: Consultancy; TeneoBio: Consultancy; Takeda: Consultancy, Research Funding; Johnson & Johnson - Janssen: Consultancy, Research Funding. Mailankody:BMS, J&J, GSK, Springworks Therapeutics: Research Funding.