Dr Feldman on the Background of the TRANSCEND CLL 004 Trial in CLL/SLL

Tatyana Feldman, MD, hematologist, director, T Cell Lymphoma Program, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale for launching the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), highlighting some of the methodologies that were used in the investigation.

The multicenter, single-arm study explored the effectiveness of lisocabtagene maraleucel (Breyanzi; liso-cel), a CAR T-cell therapy, in patients diagnosed with CLL/SLL who had experienced disease progression after treatment with both a BTK inhibitor and a venetoclax (Venclexta)–based regimen. Results from the initial analysis of this trial were previously reported, revealing notable responses to the treatment, as assessed at a median follow-up of 21.1 months (range 0.4-55.6). These findings prompted the FDA to grant priority review to a supplemental biologics license application aimed at expanding the indication of liso-cel to encompass patients with CLL and SLL who had previously received treatment with both a BTK inhibitor and a BCL-2 inhibitor.

The significance of this trial cannot be overstated, particularly in the context of the vast array of treatment options for patients with CLL, Feldman begins. These treatment options, such as BTK inhibitors and BCL-2 inhibitors, have significantly improved outcomes for patients with CLL, leading to prolonged survival and a decrease in the exhaustion of treatment options, she states. However, investigators have reached a juncture where they are witnessing relapses in patients who have received prolonged treatment, including those with extended exposure to BTK inhibitors or BCL-2 inhibitors, Feldman explains. Despite the availability of various treatment options, one of the pivotal studies shedding light on this issue is the TRANSCEND CLL 004 study, she elucidates.

Investigators reported the 24-month median follow-up analysis of TRANSCEND CLL 004 at the 2023 ASH Annual Meeting, she continues. The trial enrolled adult patients with relapsed/refractory CLL, including those who had progressed on both BTK inhibitor– and venetoclax-based treatments. Patients received liso-cel at 2 dose levels, with the second dose level deemed appropriate for all patients. The study encompassed 2 cohorts: one comprising all patients and another specific to those previously treated with venetoclax and BTK inhibitors, she concludes.