Department of Blood & Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
Doris K. Hansen , Krina K. Patel , Lauren C. Peres , Mehmet H. Kocoglu , Leyla Shune , Gary Simmons , Christopher J. Ferreri , Shebli Atrash , Ricardo Daniel Parrondo , Saurabh Chhabra , Patrick Costello , Shonali Midha , Melissa Alsina , Peter M. Voorhees , Myo Htut , Douglas W. Sborov , Jack Khouri , Murali Janakiram , Yi Lin , Surbhi Sidana
Background: Cilta-cel was FDA approved in 2022 for the treatment of RRMM. We evaluated the outcomes of patients treated with intended SOC cilta-cel. Methods: 12 US academic medical centers contributed data to this retrospective study. As of 12/31/2022, 177 patients were leukapheresed and 139 received cilta-cel. Results: The table describes the study population compared to the CARTITUDE-1 trial. More patients in our study had extramedullary disease (EMD, 35%) and high-risk cytogenetics (41%). 55% of the patients would not have met eligibility criteria for CARTITUDE-1. Common reasons for ineligibility were cytopenias (19%), prior BCMA therapy (14%), organ dysfunction (12%), oligosecretory disease (13%), and plasma cell leukemia (8%). 83% of the patients received bridging chemotherapy (overall response rate, ORR: 28%). Lymphodepletion included fludarabine (Flu) + cyclophosphamide (Cy): 81%, bendamustine: 11%, Cy: 4%, and cladribine + Cy: 4%. Median CAR-T cells infused were 0.6 million/kg (range: 0.1-0.9), and 19% of patients were treated on an expanded access protocol (EAP). Median follow-up was 2.3 months (range: 0-8). Cytokine release syndrome (CRS) was seen in 81% (≥ grade 3: 7%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 22% (≥ grade 3: 8%) of patients. Tocilizumab, steroids, and anakinra were used in 61%, 44%, and 10% of patients, respectively. Delayed neurotoxicity (NT) was seen in 9% (cranial nerve palsy: 8, Parkinsonism: 2, others: 3). Grade ≥ 3 cytopenias at day ≥ 30 were seen in 75% of patients. Infections were seen in 32% of patients. Day 30 (N=115) and best response rates (N=118) were: ≥ partial response (PR), 75/80%; ≥ very good PR, 44/62%; and ≥ complete response (CR), 26/40%, respectively. In the non-EAP FluCy population (N=88), best ORR/≥CR were 89/49%. 17 patients died by data cut-off, 4 due to disease progression and 13 (9%) due to non-relapse mortality (NRM) (grade 5 CRS: 3, infection: 6, CRS/infection: 1, grade 5 ICANS: 1, delayed NT: 2). Conclusions: Patients treated with intended SOC cilta-cel had a favorable ORR (80%) despite a larger proportion of patients having high-risk features relative to trial patients and limited follow-up. Response rates were higher in patients receiving conforming products with FluCy conditioning (89%). Delayed NT and NRM were seen in 9% of patients. Results will be updated with continued follow-up. D.K.H., K.K.P, M.J., Y.L. & S.S. contributed equally.
Intended SOC, N=139 | CARTITUDE-1, N=97 | |
---|---|---|
Median age, yrs | 64 | 61 |
ECOG PS 0 or 1 | 91% | 96% |
Extramedullary disease | 35% | 13% |
High-risk cytogenetics | 41% | 24% |
Median prior regimens | 6 (2-18) | 6 (4-8) |
Penta-refractory disease | 36% | 42% |
Grade ≥ 3 CRS and ICANS | 7%, 8% | 4%, 2% |
Delayed NT/Parkinsonism | 9%/1.4% | 12%/6% |
Best ORR/≥CR | All: 80%/40% Non-EAP FluCy: 89%/49% | 98%/83% |
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