Results of the primary analysis of a phase 1/2 study evaluating lisocabtagene maraleucel (liso-cel) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) were reported in the Lancet.
In the primary efficacy population of this study, patients receiving liso-cel showed a rate of complete response or remission, including with incomplete marrow recovery, of 18% (95% CI, 9-32; P =.0006), indicating the primary endpoint was met.
This analysis of the TRANSCEND CLL 004 study (ClinicalTrials.gov Identifier: NCT03331198) involved adults patients with R/R CLL/SLL who had received at least 2 prior lines of treatment, including a Bruton tyrosine kinase inhibitor and venetoclax. Those with high-risk cytogenetics were required to have had 2 or more prior lines of therapy, while patients with standard-risk features were required to have had 3 or more prior lines. Eligible patients also had an Eastern Cooperative Oncology Group performance status of 0 or 1.
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Liso-cel was given as an infusion of either 50 x 106 chimeric antigen receptor (CAR) T-cells (dose level 1; DL1) or 10 0x 106 CAR T-cells (dose level 2; DL2). In this analysis, the primary efficacy endpoint of complete response or remission, including with incomplete marrow recovery, involved efficacy-evaluable patients treated at DL2 and was based on assessment by an independent review committee (IRC).
There were 137 patients who underwent leukapheresis and 117 patients who were treated with liso-cel overall. In the treated population, the median age was 65 years, and patients had received a median of 5 prior lines of therapy (interquartile range, 3-7). Of these patients, there were 49 who were treated at DL2 and included in the primary efficacy analysis. Among these patients, 9 (18%; 95% CI, 9-32) reached complete response/remission, including with incomplete marrow recovery, per IRC review.
In the full safety population of 117 patients, it was reported that cytokine release syndrome (CRS) of grade 3 was observed in 9% of patients, without any grade 4 or 5 CRS events.
Regarding neurological events, these reportedly occurred at grade 3 in 18% of patients and at grade 4 in 1%. There were 5 deaths attributed to treatment-emergent adverse events, 1 of which was considered related to liso-cel infusion.
The study investigators concluded that durable complete response/remission was seen in patients of this study population following liso-cel treatment. They also considered liso-cel to have demonstrated a manageable safety profile.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Reference
Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. Published online June 5, 2023. doi:10.1016/S0140-6736(23)01052-8.
