Dr. Wierda on the Safety and Efficacy Results of the TRANSCEND CLL 004 Trial in CLL

William G. Wierda, MD, PhD, professor, D.B. Lane Cancer Research Distinguished Professor, section chief of Chronic Lymphocytic Leukemia, center medical director, Department of Leukemia, Division of Cancer Medicine, and executive medical director, Inpatient Medical Services, The University of Texas MD Anderson Cancer Center, discusses the safety and efficacy results of the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in chronic lymphocytic leukemia (CLL).

During the 2021 International Workshop on CLL, findings from cohort 1 of the TRANSCEND CLL 004 trial were presented. The cohort included 23 patients with relapsed/refractory CLL or small lymphocytic lymphoma who progressed on ibrutinib (Imbruvica) at enrollment, had high-risk features and received ibrutinib for at least 6 months with less than a complete response (CR), or harbored BTK or PLCγ2 mutations. Patients could undergo bridging therapy prior to lymphodepletion and treatment with the combination of lisocabtagene maraleucel (liso-cel; Breyanzi) and ibrutinib. Moreover, 19 patients received liso-cel at 50 x 10⁶ CAR+ T cells and 4 received liso-cel at 100 x 10⁶ CAR+ T cells.

Regarding safety, grade 3 cytokine release syndrome (CRS) was observed in 4% of patients and no events occurred with the higher dose of liso-cel, Wierda says. Grade 3 neurotoxicity was reported in 17% of patients. Notably, CRS and neurotoxicity events were manageable with steroids and/or tocilizumab (Actemra) intervention, Wierda explains.

In the overall population, the combination of liso-cel and ibrutinib induced a CR rate of 59% and a partial response rate of 36%. Moreover, 86% of patients achieved undetectable minimal residual disease (MRD) in the peripheral blood by flow cytometry, and 86% achieved undetectable MRD in the bone marrow by next-generation sequencing.

As such, the combination elicited significant activity in this relapsed/refractory patient population and potentially predicts for earlier integration of CD19-directed CAR T-cell therapies into the treatment armamentarium of patients with CLL, Wierda concludes.