Lisocabtagene Maraleucel (liso-cel) in Patients (Pt) With R/R CLL/SLL: 24-Mo Median Follow-up of TRANSCEND CLL 004

Background Pts with R/R CLL/SLL after Bruton tyrosine kinase inhibitor (BTKi) and venetoclax treatment have no established standard of care and poor outcomes. Here, we report results from the phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study of liso-cel in R/R CLL/SLL with a median follow-up of 23.5 mo. Methods Pts with R/R CLL/SLL and ≥ 2 prior lines of therapy, including a BTKi (full population), received liso-cel at a target dose of 50 × 106 (dose level [DL] 1) or 100 × 106 (DL2) CAR+ T cells. The primary endpoint was complete response/remission (CR) including CR with incomplete marrow recovery (CRi) by an independent review committee (IRC) per 2018 International Workshop on CLL (iwCLL) criteria in the prespecified subset of efficacy-evaluable pts with disease progression on BTKi and venetoclax failure (primary efficacy analysis set [PEAS]) at DL2. Results Of 137 leukapheresed pts, 118 received liso-cel (safety set), 97 (DL1 = 9; DL2 = 88) were efficacy evaluable, and 54 (DL1 = 4; DL2 = 50) were in the PEAS. In the safety set, median (range) age was 65 y (49–82), 83% had high-risk cytogenetics, median (range) lines of prior therapy were 5 (2–14), and all pts had prior BTKi. As of data cutoff (February 28, 2023), median (range) on-study follow-up was 23.5 mo (0.4–59.6). Efficacy outcomes in the PEAS are in Table 1. One pt with best overall response (BOR) of partial response/remission (PR) at primary analysis had deepened to CR/CRi at 18 mo without any additional therapy. Of 9 pts with BOR of CR/CRi at the primary analysis, 8 had ongoing CR/CRi and 1 completed the study with the last assessment as CR/CRi. Efficacy outcomes were similar in the full population at DL2. Of 16 pts who had BOR of CR/CRi at primary analysis, 10 had ongoing CR/CRi. In the safety set, rates of any-grade (gr) and gr ≥ 3 treatment-emergent AEs were similar across age groups (Table 2). The rate of any-gr cytokine release syndrome (CRS) was 85% (gr 3, 8%; no gr 4/5) and neurological events (NE) was 45% (gr 3, 18%; gr 4, 1%; no gr 5); 69% received tocilizumab and/or corticosteroids for CRS/NEs. Median (range) time to onset and resolution was 4 d (1–18) and 6 d (2–37) for CRS and 7 d (1–21) and 7 d (1–83) for NEs, respectively. Prolonged cytopenia (gr ≥ 3 at D30 after infusion), gr ≥ 3 infections, hypogammaglobulinemia, tumor lysis syndrome, second primary malignancy, and macrophage activation syndrome occurred in 54%, 18%, 15%, 11%, 9%, and 3%, respectively. Forty-four (37%) of 118 liso-cel–treated pts died after infusion (disease progression, n = 26 [22%]; AE, n = 6 [5%]; other reasons, n = 12 [10%]). Conclusions With longer follow-up, liso-cel continued to demonstrate durable CR/CRi, high uMRD rates, and a manageable safety profile in pts with heavily pretreated, high-risk R/R CLL/SLL. The safety results from longer follow-up were similar to those reported in the primary analysis with no new safety signals and were consistent across age groups.