Results from a cohort of the TRANSCEND CLL 004 study found that the combination of lisocabtagene maraleucel (liso-cel) and ibrutinib for the treatment of relapsed or refractory chronic lymphocytic leukemia /small lymphocytic lymphoma was efficacious, inducing deep and durable responses, with a manageable safety profile.
William G. Wierda, MD, of the University of Texas MD Anderson Cancer Center, and colleagues, published the findings in Blood.
The researchers reported on data from a cohort of patients who received liso-cel plus ibrutinib in the multicenter, open-label, phase 1/2 study.
A total of 65 adult patients were enrolled in this treatment cohort between August 16, 2018, and November 23, 2021, with 56 patients (86%) receiving liso-cel and ibrutinib. Most patients (98%; n=55) had high-risk cytogenetics and received a median of five prior lines of therapy, including 55% who progressed after prior Bruton’s tyrosine kinase inhibitor and venetoclax failure.
At data cutoff, 28 patients (50%) discontinued the study, 11 (20%) completed the study, and 17 (30%) were still ongoing in the study. Median on-study follow-up was 24.8 months.
Efficacy was assessed in 51 patients who received liso-cel dose level two (100×10−6 cells/kg). The complete response (CR)/CR with incomplete marrow recovery (CRi) rate (primary endpoint) was 45% (n=23) and the overall response rate (secondary endpoint) was 86% (n=44). Median time to first response was one month.
The undetectable minimal residual disease at 10−4/span> sensitivity (uMRD4) rate was 86% in peripheral blood (PB) and 84% in bone marrow (BM). Among patients who achieved CR/CRi, uMRD4 was 96% in both PB and BM.
Half of patients (n=11) who experienced CR/CRi did so as first response, while the other half (n=12) had partial responses that deepened to CR/CRi.
Median progression-free survival (PFS) was 31.4 months, and overall survival (OS) was not reached. At 24 months, PFS and OS rates were 62% and 80%, respectively. Median duration of response was 41.4 months, with a 24-month probability of continued response of 65.0%.
Most patients (n=46; 86%) experienced grade ≥3 treatment-related adverse events, most commonly neutropenia (52%) and anemia (41%). Five hemorrhage events were reported.
Eighteen patients died, with primary causes being progression (n=6), unknown (n=6), COVID-19 infection (n=3), and mixed septic/cardiogenic shock (n=1).
Cytokine release syndrome occurred in 45 patients (80%), two of which were grade 3. Neurological events occurred in 23 patients (41%), and eight patients (14%) experienced grade 3 infections. Overall, no new safety signals emerged.
The researchers compared patients who received liso-cel plus ibrutinib versus a cohort that received liso-cel monotherapy and the data “suggest that ibrutinib treatment may reduce exhaustion in CAR T cells after infusion and are among the first data demonstrating that combination treatment can directly improve CAR T-cell function in patients, translating into improved responses.”
However, they note that the differences in study design and patient population between these cohorts preclude any direct comparisons.
The study was funded by Juno Therapeutics, a Bristol Myers Squibb Company.
Reference
Wierda WG, Dorritie KA, Gauthier J, et al. Lisocabtagene maraleucel combined with ibrutinib in R/R CLL or SLL: primary results from TRANSCEND CLL 004. Blood. 2026. doi:10.1182/blood.2026033565
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