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Idecabtagene Vicleucel (ide-cel) Chimeric Antigen Receptor T-Cell for Plasma Cell Leukemia (PCL): A Multicenter Experience

Year: 2024

Type: article

Abstract: Despite improvements in long-term outcomes of patients (pts) with multiple myeloma, the prognosis of pts with plasma cell leukemia (PCL) remains poor. We conducted a multicenter retrospective analysis of pts with history of PCL undergoing leukapheresis for standard of care (SOC) ide-cel. This IRB-approved multicenter study identified PCL pts who underwent leukapheresis for ide-cel before Dec 31, 2022. PCL was defined as the presence of ≥ 5% plasma cells (PCs) in the peripheral blood and pts were categorized as having primary (pPCL) or secondary PCL (sPCL). Progression-free survival (PFS) and overall survival (OS) were calculated from date of infusion to date of progression or death using the Kaplan-Meier method. 15 pts underwent leukapheresis (Table 1). At a median follow-up of 6 mo (Range 0-15), 11 pts received ide-cel. The 4 remaining pts died secondary to disease-related complications at a median of 34.5 d (range 5-59) following leukapheresis. The median age was 61 years, 73% had high-risk cytogenetics (t(14;16), t(4;14), 1q21 gain or amp, and del17p), 33% had t(11;14), and 73% were categorized as sPCL. Overall, 6 pts (40%) had circulating PCs at the time of leukapheresis with a median of 14.5% PCs (range 1 - 48). The median number of prior therapies was 6 (range 4 - 9), all pts were triple-class refractory, 40% were penta-class refractory, and 80% required bridging therapy. All pts with pPCL (n = 4) and 64% (n = 7) sPCL patients were infused. No pPCL and 3 (43%) sPCL pts had circulating PCs at lymphodepletion (LD). The median CAR-T cell dose infused was 413 (range 331-455) million cells. 81% of pts experienced any grade CRS (11% grade 3, no grade 4 or 5), 36% had ICANS (all grade 1), and 55% had infection. At d +90, regarding any grade cytopenias, 45% had neutropenia, 73% had anemia, and 54% had thrombocytopenia; 72% required G-CSF support and 27% required TPO agonist. All 4 pPCL pts responded (2 PR, 1 VGPR, and 1 sCR) and 4 sPCL pts responded (1 PR, 2 VGPR, and 1 CR) to ide-cel per IMWG criteria (Figure 1); the median time to best response was 30 days (range 14-91). In the overall cohort, the mPFS was 3.7 months (95% CI 2.8-NR months) and mOS 6.7 months (95% CI 4.6-NR months). There was no difference in mPFS between pPCL and sPCL pts (HR 2.79, 95% CI 0.56-13.8, p=0.2) or those with or without circulating PCs at LD (HR 3.87, 95% CI 0.77-19.5, p=0.10) but pts with sPCL had shorter mOS than those with pPCL (4.6 vs. 8.1 mo (HR 9.15, 95% CI 1.09 - 77.0, p=0.042)) as did those with circulating PCs at LD compared to those without (2.9 vs. 7.1 mo, HR 12.4, 95% CI 1.26-123, p=0.031) (Figure 2). In our study, across the entire PCL cohort, responses were evident but not prolonged in the majority of patients and survival was longer for patients with pPCL and in those without circulating PCs at the time of lymphodepleting chemotherapy. Our results suggest that Ide-cel is a feasible treatment option but outcomes remain dismal.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.534