Lisocabtagene Maraleucel Shows ‘Durable’ CRs in TRANSCEND CLL 004 Trial

Lisocabtagene maraleucel demonstrated “durable” complete responses (CR) and a “manageable safety profile” in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to the primary analysis of the phase I/II TRANSCEND CLL 004 study.

Tanya Siddiqi, MD, of the City of Hope National Medical Center and colleagues presented results from the primary analysis during the 2023 American Society of Clinical Oncology Annual Meeting.

The study included patients who received at least two prior lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor (n=117). Patients who progress on a BTK inhibitor and experience treatment failure with venetoclax-based regimens do not often achieve a CR with current treatment regimens, according to the study’s authors.

“For people living with relapsed or refractory CLL or SLL after treatment with BTK [inhibitor] and BCL2 [inhibitor]-based regimens, there is no standard of care treatment. Achieving deep and lasting remission in this situation is challenging as most patients experience disease progression despite continuous treatment,” Dr. Siddiqi said in a news release. “The durable complete responses observed with [lisocabtagene maraleucel] in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T-cell-based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease.”

The study’s primary endpoint was the rate of CR and CR with incomplete marrow recovery (CRi) in a prespecified subset of patients. The prespecified subset included efficacy-evaluable patients who received a dose of 100×10⁶ chimeric antigen receptor (CAR) T cells and had disease progression on a BTK inhibitor, as well as venetoclax treatment failure (n=49). Key secondary endpoints were the overall response rate (ORR) and the rate of undetectable minimal residual disease (MRD) in blood.

The study met its primary endpoint, as the CR rate was 18.4% in the prespecificed subset of patients for the analysis (95% CI, 8.8-32.0; one-sided P=.0006). Among patients who achieved a CR, no disease progression or deaths were reported. The median duration of CR was not reached at a median follow-up of 21.1 months.

The ORR was 42.9%, with a median duration of response of 35.3 months at a median follow-up of 19.7 months.

In the 117 patients who were evaluable for safety, any grade of cytokine release syndrome (CRS) occurred in 84.6% of patients, with no grade 4 or 5 CRS reported. Neurological events occurred in 45.3% of patients, with no grade 5 neurological events reported. The researchers reported grade 3 or higher infections in 17.9% of patients, hypogammaglobulinemia in 15.4%, and prolonged cytopenia in 53.8%. One death related to lisocabtagene maraleucel was due to hemophagocytic lymphohistiocytosis.

The CAR-T therapy “demonstrated durable CR/CRi, high [undetectable] MRD rates, and a manageable safety profile” in patients with heavily pretreated, high-risk relapsed or refractory CLL/SLL and “high unmet need,” Dr. Siddiqi and colleagues concluded.

Funding for the study was provided by Juno Therapeutics, a Bristol-Myers Squibb Company.

Reference

Siddiqi T, Maloney DG, Kenderian S, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004. Abstract #7501. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.