2004 - Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): primary analysis of TRANSCEND CLL 004

Introduction: In patients with relapsed or refractory (R/R) CLL/SLL that progressed on Bruton tyrosine kinases inhibitor (BTKi) and failed venetoclax-based regimens, achieving complete response (CR) with current treatment is uncommon. New therapies that achieve deep and durable responses are needed. We report the primary analysis of the phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study evaluating liso-cel in patients with R/R CLL/SLL.

Methods: Patients must have received at least 2 prior lines of therapy, including a BTKi. Eligible patients received liso-cel at a target dose of either 50 (dose level [DL] 1) or 100 (DL2) × 10⁶ chimeric antigen receptor–positive T cells. The primary endpoint was rate of CR and CR with incomplete marrow recovery (CRi) by independent review committee per 2018 International Workshop on Chronic Lymphocytic Leukemia criteria in the prespecified subset of efficacy-evaluable patients with disease progression on BTKi and venetoclax failure (primary efficacy analysis set [PEAS]) at DL2 (null hypothesis [H0]: ≤ 5%). Key secondary endpoints were overall response rate (ORR; H0: ≤ 40%) and rate of undetectable minimal residual disease (uMRD; 10⁻⁴) in blood (H₀: ≤ 5%).

Results: Of 137 leukapheresed patients, 117 received liso-cel (safety set), 96 (DL1 = 9; DL2 = 87) were efficacy evaluable, and 53 (DL1 = 4; DL2 = 49) were in the PEAS. In the safety set, median (range) age was 65 years (49–82), 83% had high-risk features, median (range) lines of prior therapy was 5 (2–12), and all patients had prior BTKi. Median (range) on-study follow-up was 21.1 months (0.4–55.6) for the safety set. In the PEAS at DL2, the primary endpoint of CR/CRi rate was met at 18.4% (95% confidence interval [CI], 8.8–32.0; 1-sided P = 0.0006; Table). ORR was 42.9% and was not statistically significant (95% CI, 28.8–57.8; 1-sided P = 0.3931). The uMRD rate was 63.3% in blood and 59.2% in marrow. Median (95% CI) duration of response was 35.3 months (11.01–not reached [NR]) with a median follow-up of 19.7 months. Median duration of CR/CRi was NR. In the safety set, rate of any-grade cytokine release syndrome (CRS) was 84.6% (grade 3, 8.5%; no grade 4/5) and neurological events (NE) was 45.3% (grade 3, 17.9%; grade 4, 0.9%; no grade 5); 69.2% received tocilizumab and/or corticosteroids for CRS/NEs. Rate of grade ≥ 3 infections, hypogammaglobulinemia, and prolonged cytopenia was 17.1%, 15.4%, and 53.8%, respectively. One death related to liso-cel was due to hemophagocytic lymphohistiocytosis. Liso-cel exhibited rapid in vivo expansion and was detected by quantitative polymerase chain reaction in blood up to 36 months after infusion.

Conclusions: Liso-cel demonstrated durable CR/CRi, high uMRD rates, and a manageable safety profile in patients with heavily pretreated, high-risk R/R CLL/SLL and high unmet need.