OA – 11: Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel (Cilta-cel) for Relapsed/Refractory Multiple Myeloma (RRMM): Real World Experience With Updated Follow-up
Friday, September 27, 2024
10:12 AM – 10:24 AM East Coast USA Time
Location: Rio de Janeiro Ballroom, Lagune Barra Hotel
Assistant Professor Stanford University, United States
Introduction: We present updated outcomes of patients with relapsed/refractory multiple myeloma (RRMM) treated with standard of care ciltacabtagene autoleucel (cilta-cel), with longer follow-up and expanded patient cohort.
Methods: Patients at 16 US academic centers who underwent apheresis with intention to manufacture standard of care cilta-cel by 12/31/2022 were included.
Results: 255 patients underwent apheresis and 236 (92.5%) received cilta-cel infusion. 19 patients did not get cilta-cel due to progression/death (11), manufacturing failure (3), other cancer (2) or other reasons (3). Median CAR-T cell dose (106/kg) was 0.6 (0.1-1); cell dose < 0.4 x 106/kg: n=7. 19% of patients received a non-conforming product. The median follow-up after CAR-T was 13 months (range: 0.3-21.8).
Amongst patients receiving cilta-cel (N=236), median age was 64 years (26% ³ 70 years), 57% were male, 30% had penta-refractory disease, 34% had extramedullary disease (EMD), 39% had high-risk cytogenetics, and 6% had plasma cell leukemia. Median prior lines of therapy were 6, 14% had prior BCMA therapy and 4% had prior bispecific antibodies. 54% of the patients would not have met eligibility criteria for CARTITUDE-1. 78% of the patients received bridging chemotherapy (overall response rate, ORR: 27%). Lymphodepletion (LD) included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 13%, others: 6%.
Cytokine release syndrome occurred in 75% (≥ grade 3: 5%), immune effector cell-associated neurotoxicity syndrome in 14% (≥ grade 3: 4%) and HLH-like syndrome in 2% of patients. Delayed neurotoxicity (DNT) occurred in 10% of patients with median time to onset of 24 days, with most common finding being 7th nerve palsy (4%, n=11) and Parkinsonism seen in 2% (n=5) patients. DNT resolved in 54% of patients by last follow-up, while 21% patients died with ongoing symptoms. Severe infections were seen in 21% of patients. Second primary malignancies (SPMs) were seen in 8.5%. SPMs excluding non-melanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%.
Overall response rate (ORR) and complete response (CR) rates were 89% and 70% in all infused patients, and 95% and 76% in patients receiving a conforming product with Flu/Cy lymphodepletion. Median progression free survival was not reached, with a 12-month survival estimate of 68% (95% CI: 62-74) in all patients and 73% (95% CI: 66-81) in patients with conforming product and Flu/Cy LD. Patients with prior BCMA therapy, high-risk cytogenetics, and extramedullary disease had inferior PFS on multivariable analysis. 50 patients died by data cut-off, including 10% (n=23) due to non-relapse mortality.
Conclusions: Patients treated with SOC cilta-cel had a favorable ORR (89%), CR rate (70%) and PFS with longer follow-up (12 month estimate: 68%) despite a large proportion of patients having high-risk features. Long-term monitoring for SPMs is recommended.
