P-049: Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel (Cilta-cel) for Relapsed/Refractory Multiple Myeloma (RRMM): Real World Experience
Assistant Professor Stanford University, United States
Introduction: In this multi-center study, we evaluated the outcomes of patients treated with intended standard of care cilta-cel.
Methods: Patients at 14 US academic centers who underwent apheresis with intention to manufacture cilta-cel by 9/15/2022 were included. Data cut-off was April 1, 2023.
Results: 153 patients underwent apheresis and 143 (94%) received cilta-cel infusion. 10 patients did not get cilta-cel due to progression/death (6), myelodysplastic syndrome (1), manufacturing failure (1), OOS product declined by patient (1) and lost to follow up (1).
Amongst patients receiving cilta-cel (N=143), median age was 64 years, with 27% being above age 70; 57% were male, 34% had penta-refractory disease. Compared to CARTITUDE-1 study population, our cohort had higher incidence of extramedullary disease (EMD, 31% vs 13%) and high-risk cytogenetics (41% vs 24%). 57% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (17%), prior BCMA therapy (15%), organ dysfunction (12%), poor performance status (11%) and plasma cell leukemia (7%). 80% of the patients received bridging chemotherapy (overall response rate, ORR: 30%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 84%, bendamustine: 9%, Cy: 3.5%, and cladribine + Cy: 3.5%. Median CAR-T cells infused were 0.6 million/kg, and 22% of patients were treated on expanded access protocol (EAP). Median follow-up was 6 months.
Cytokine release syndrome (CRS) was seen in 80% (≥ grade 3: 5%), immune effector cell-associated neurotoxicity syndrome (ICANS) in 18% (≥ grade 3: 6%) and hemophagocytic lymphohistiocytosis (HLH)-like syndrome in 3% of patients. Tocilizumab, steroids, and anakinra were used in 61%, 41%, and 13% of patients, respectively. Delayed neurotoxicity (NT) was seen in 12% (n=17; 7th cranial nerve palsy: 9, Parkinsonism: 2, others: 6), with median time to onset being 25 days. It resolved in 6 patients by last follow-up, while 3 patients died with ongoing delayed NT. Infections were seen in 37% of patients.
Day 30 (N=134) and best response rates (N=140) were: ≥ partial response (PR), 81/89%; very good PR, 51/77%; and complete response (CR), 29/56%, respectively. In the non-EAP FluCy population (N=92), ORR/≥CR were 94/61%. Median progression free survival was not reached, with 6-month estimate being 79%. 22 patients died by data cut-off, including 14 (10%) due to non-relapse mortality (infection:6, grade 5 CRS:3, CRS/infection:1 grade 5 ICANS:1, delayed NT:2, HLH:1).
Conclusions: Patients treated with SOC cilta-cel had a favorable ORR (89%) and CR rate (56%) despite a larger proportion of patients having high-risk features relative to trial patients. Response rates were higher in patients receiving conforming products with FluCy conditioning (94%). Delayed NT was seen in 12% and non-relapse mortality in 10% of patients, respectively.
