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Lisocabtagene Maraleucel (liso-cel) in Patients (Pts) with Relapsed or Refractory (R/R) Mantle Cell Lymphoma (MCL): Results from the Final Analysis of the MCL Cohort of the Open-Label, Phase 1, Seamless Design, Multicenter Transcend NHL 001 (TRANSCEND) Study

Year: 2025

Type: article

Abstract: Introduction At the primary analysis (PA) of the TRANSCEND (NCT02631044) MCL cohort, liso-cel showed high efficacy (ORR, 83%; CR rate, 72%) at a median follow-up of 16.1 mo, with durable responses (median duration of response [DOR], 15.7 mo) and sustained PFS (median, 15.3 mo) and OS (median, 18.2 mo) in the efficacy analysis set (EAS) and low rates of grade (gr) ≥ 3 cytokine release syndrome (CRS; 1%), neurological events (NE; 9%), and infections (15%) in pts with R/R MCL (Wang M, et al. J Clin Oncol 2024). Objectives Report results from the final analysis, when all pts from the TRANSCEND MCL cohort had completed or discontinued the study. Methods The TRANSCEND MCL cohort enrolled adults with R/R, PET-positive MCL after ≥ 2 prior lines of systemic therapy including Bruton tyrosine kinase inhibitor (BTKi), alkylating, and CD20-targeted agents. Primary endpoints included AEs and ORR by independent review committee (IRC) per Lugano 2014 criteria. Efficacy is reported in the EAS, defined as liso-cel–treated pts with PET-positive disease at baseline per IRC. Safety is reported in the liso-cel–treated set, defined as all pts with ≥ 1 dose of liso-cel. After completing or discontinuing the study, pts were to enroll in a separate long-term follow-up (LTFU) study (NCT03435796) assessing safety and OS for up to 15 y after liso-cel. Results are summarized descriptively. Results A total of 88 pts received liso-cel. All pts completed the study (including 10 pts ongoing at the PA) or discontinued earlier; 29 pts have enrolled to LTFU. Median follow-up including LTFU was 19.5 mo (range, 0.4–72.0). In the EAS (n = 83), liso-cel continued to show clinical benefit, with consistently high efficacy (ORR, 83%; CR rate, 72%) and durable responses (median DOR, 14.5 mo) with sustained PFS (median, 12.3 mo) and OS (median, 18.4 mo) ( Table 1 ), as in the PA. Among leukapheresed pts (n = 104), 48 died after product infusion, mostly due to PD (n = 31) with no new deaths since the PA. Safety in the liso-cel–treated set was also consistent with the PA, with no new safety signals ( Table 2 ). Rates of any-gr and gr ≥ 3 treatment-emergent (TE; occurring ≤ 90 d after liso-cel) AEs were unchanged from the PA. Rates of TE gr ≥ 3 CRS, gr ≥ 3 NEs, gr ≥ 3 infections, second primary malignancies (SPM), and prolonged cytopenias also remained low and consistent with the PA. In the post-TE period (> 90 d after liso-cel; n = 82), 45 (55%) pts had any-gr AEs (gr ≥ 3, n = 25 [30%]); 14 pts (17%) had SPMs, including 1 additional pt since the PA who developed myelodysplastic syndrome , considered related to lymphodepleting chemotherapy. Conclusion In the final analysis of the TRANSCEND MCL cohort, efficacy and safety were consistent with the PA with continued responses (24-mo DOR, 42%) and no new safety signals. These data support the sustained clinical benefit and favorable benefit/risk profile of liso-cel in pts with R/R MCL after ≥ 2 prior lines of systemic therapy, including BTKi.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.jtct.2025.01.319