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Lisocabtagene Maraleucel (liso-cel) in Patients (Pt) with R/R MCL: Subgroup Analyses in Pts with High-Risk Disease Features from the MCL Cohort of the TRANSCEND NHL 001

Year: 2024

Type: article

Abstract: In R/R MCL, several high-risk features are associated with a worse prognosis including TP53 mutation, high Ki-67 proliferation index, blastoid morphology, and secondary CNS involvement. We report outcomes from prespecified subgroup analyses based on high-risk features from the MCL cohort of TRANSCEND NHL 001 (NCT02631044) of liso-cel in pts with R/R MCL. Pts had PET-positive R/R MCL after ≥ 2 lines of prior therapy, including Bruton tyrosine kinase inhibitor (BTKi), alkylating agent, and CD20-targeted agent. Pts received liso-cel at a target dose of 50 × 106 or 100 × 106 CAR+ T cells after lymphodepleting chemotherapy. Bridging therapy was allowed. Primary endpoints were treatment-emergent AEs (TEAE) and ORR by independent review committee (IRC; Lugano 2014 criteria); secondary endpoints included CR rate, duration of response (DOR), PFS, and OS. A total of 88 pts received liso-cel. Median on-study follow-up was 16.1 mo (range, 0.4–60.5). Median age was 68.5 y (range, 36–86). Median prior systemic lines of therapy was 3 (range, 1–11). Among liso-cel–treated pts, 75% had Ki-67 ≥ 30% and 17% had Ki-67 < 30% (not reported, 8%), 23% had TP53 mutation and 39% did not (indeterminate, 5%; not reported, 34%), and 31% had blastoid morphology and 55% did not (not reported, 15%). Most pts with high-risk features also had disease refractory to last therapy and/or to prior BTKi and had complex karyotype. Seven (8%) pts had secondary CNS lymphoma (refractory disease, n = 5; Ki-67 ≥ 30%, n = 5; TP53 mutation, n = 1; blastoid morphology, n = 1). Response rates, PFS, and OS across subgroups were consistent with the overall population, with high ORR, durable CR rate, and high PFS and OS (Table 1). Of pts with TP53 mutation assessed, pts with mutation had a numerically lower median DOR than the overall population, likely due to more responders achieving a PR than CR. However, of 11 pts with TP53 mutation who achieved CR, 6 were in ongoing response at cutoff. Among pts with secondary CNS lymphoma, ORR was 86%, CR rate was 71%, and 3 of 5 pts with CR were in ongoing response at cutoff. Safety across subgroups was generally consistent with the overall population (Table 2). Among subgroups, TEAEs of special interest rates were similar, and most cytokine release syndrome (CRS) and neurological events (NE) were low grade. Of the 7 pts with secondary CNS lymphoma, 5 had low-grade CRS and 3 had low-grade NEs with no grade ≥ 3 CRS or NEs; 1 pt had a grade ≥ 3 infection. In subgroup analyses including pts with R/R MCL and high-risk features, liso-cel showed clinically meaningful efficacy across subgroups with durable responses. Efficacy and safety were generally consistent with the overall population. While some subgroups had small numbers, results suggest a favorable benefit/risk profile for liso-cel in pts with R/R MCL and high-risk features, a population for whom effective treatment options are rarely available.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2023.12.037