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    Cellular and T cell engager Immunotherapy

    Category: Cellular and T cell engager Immunotherapy

    Safety and Efficacy of Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma: A CIBMTR Study

    (PA-002) Safety and Efficacy of Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma: A CIBMTR Study

    Thursday, September 18, 2025

    • Doris K. Hansen, MD

      Hematologist/Oncologist
      Department of Blood & Marrow Transplant and Cellular Immunotherapy (BMT CI), Moffitt Cancer Center

    Introduction: Ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, was approved in 2022 for relapsed/refractory multiple myeloma (RRMM). This study evaluates the safety and efficacy of cilta-cel in standard-of-care (SOC).

    Methods: The study cohort included RRMM patients in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry who received SOC cilta-cel between April 2022 and December 2023, meeting commercial release specifications. Multivariable analyses of predictors for grade ≥ 2 cytokine release syndrome (CRS) and survival were conducted using logistic and Cox regression models, respectively.

    Results:

    Among 595 patients who received cilta-cel, median age was 64 years, 57% (n=340) were male, and 70% had ≥1 clinically significant comorbidity (n=416). Penta-class exposure occurred in 55% (n=328), International Staging System (ISS) ≥ II in 41% (n=106/260), and high-risk cytogenetics in 27% (n=142/530). Extramedullary disease and marrow plasma cell burden (PCB) ≥ 50% were present in 13% (50/382) and 14% (n=54/373) of patients, respectively. The median number of prior lines of therapy was 7 (range, 4-24), with 5 patients receiving prior CAR-T and 8% (n=45) prior BCMA therapy: 6% (n=37) belantamab mafodotin, 1% (n=7) teclistamab, or a combination of both (n=1). Lymphodepletion included fludarabine/cyclophosphamide (78%, n=461), bendamustine (19%, n=111), and others. Median follow-up was 12 months (range, 1-25 months).



     



    CRS occurred in 80% (n=475, ≥ grade 3: 4%), immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (n=133, ≥ grade 3: 4%) and immune-effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome in 4% (n=21). Non-ICANS neurotoxicity was seen in 5% (n=31), including Parkinsonism in 2.7% (n=16) and cranial nerve (CN) palsies in 2.5% (n=15), primarily CN VII (n=12/15). Clinically significant infections were seen in 47% (n=281) of patients. Multivariable analysis identified PCB ≥ 50% as an independent risk factor for grade ≥ 2 CRS.



     



    The best overall response rate was 87%, very good partial response rate was 40%, and complete response (CR)/stringent CR rate was 35%. Estimated 12-month progression-free survival (PFS) and overall survival were 73% (95% CI: 68-77%) and 85% (95% CI: 81-88%), respectively. Male sex, high-risk cytogenetics, prior BCMA therapy, ECOG PS ≥2, PCB ≥ 50%, elevated baseline lactate dehydrogenase, and ferritin ≥ 150 ng/mL were associated with inferior PFS on multivariable analysis. At last follow-up, 15% (n=91) of patients have died, including 5% (n=27) due to non-relapse mortality, most commonly from infections (44%, n=12).


    Conclusions:

    This is the largest SOC study of cilta-cel in heavily pretreated RRMM patients. Safety and efficacy profiles were favorable and support its use in clinical practice, despite patient heterogeneity and a high prevalence of clinically significant comorbidities.