Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM).

Abstract

8012 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. [Table: see text]

Autologous hematopoietic stem cell transplantation for multiple myeloma in the age of CAR T cell therapy

“…Notably, 22% of patients included in this dataset were infused with an out of specification (OOS) cilta-cel product. The presence of high-risk cytogenetics (defined as the presence of del17p, t[4;14)], or t[14;16]) was associated with poorer ORR, PFS, and OS in multivariate analysis ( 43 ).…”

“…Tocilizumab is generally only used if patients have coexisting CRS ( 50 , 51 ). ICANS typically manifests later than CRS (around day 2-3 with ide-cel and days 8-10 with cilta-cel) ( 11 – 14 , 36 , 43 ). An additional neurologic toxicity seemingly unique to cilta-cel is less well understood.…”

Utilizing 3D Models to Unravel the Dynamics of Myeloma Plasma Cells’ Escape from the Bone Marrow Microenvironment

“…Notably, the integration of these novel agents into frontline therapy, maintenance, and relapse settings has led to prolonged survival rates and deeper remissions [ 10 ]. Additionally, the emergence of chimeric antigen receptor T-cell (CAR-T) therapy represents a ground-breaking advancement, particularly for relapsed/refractory multiple myeloma (RRMM), showcasing remarkable efficacy in clinical trials and reproducible in real-world settings [ 11 , 12 , 13 , 14 , 15 , 16 ]. More recently, T-cell engaging (TCE) therapies have also been approved and are available in a similar population of patients with RRMM after exposure to greater than or equal to four prior lines of therapy [ 17 , 18 , 19 ].…”

CAR T‐Cell Therapy for Multiple Myeloma: A Clinical Practice‐Oriented Review

“…Following propensity score matching and intention‐to‐treat analysis, the cilta‐cel group showed improved ORR (84% vs. 28%, P < 0.001), PFS (HR, 0.11, 95% CI, 0.05–0.22), and OS (HR, 0.20, 95% CI, 0.10–0.39) compared with the MAMMOTH cohort 50 . Later on, a real‐world experience of 12 US academic centers showed an ORR of 80% among patients treated with standard‐of‐care cilta‐cel, despite a larger proportion of patients having high‐risk features relative to trial patients and limited follow‐up 51 …”