Phase I/II TRANSCEND CLL 004 trial: Liso-cel + ibrutinib in R/R CLL/SLL

Results from the open-label, multicenter, phase I/II TRANSCEND CLL 004 trial (NCT03331198/NCT03435796) evaluating lisocabtagene maraleucel (liso-cel) + ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) were published in Blood by Wierda et al. Patients received liso-cel at 50 × 10⁶ (dose level [DL]1; n = 5) or 100 × 10⁶ (DL2; n = 51) chimeric antigen receptor-positive (CAR+) T cells with concurrent ibrutinib from enrollment through 90 days after liso-cel infusion or longer per investigator discretion. The primary endpoint was complete response (CR) / CR with incomplete marrow recovery (CRi) rate by investigator assessment in the DL2 group. Safety was assessed in the DL1 + DL2 groups.

Key data: In the DL2 group, the CR/CRi rate was 45% (95% confidence interval [CI], 31–60) and the overall response rate (ORR) was 86% (95% CI, 74–94). In post hoc analyses, among patients who received DL2 and who had undetectable measurable residual disease at 10⁻⁴ sensitivity (uMRD4) in the peripheral blood (PB), median progression-free survival (PFS) was 31.4 months (95% CI, 20.1–not reached [NR]). In DL1 + DL2, Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 86% of patients, most commonly neutropenia (52%) and anemia (41%). Cytokine release syndrome (CRS) occurred in 80% of patients (Grade 3, 4%; no Grade 4/5), and neurological events (NE) in 41% (Grade 3/4, 11%; no Grade 5).

Key learning: Liso-cel + ibrutinib demonstrated notable efficacy in patients with R/R CLL/SLL with a manageable and predictable safety profile and no new safety signals, supporting its continued evaluation as a treatment option in this population.