Dr Feldman on Updated Findings From 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 updated safety and efficacy data from the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

The single-arm, multicenter study investigated the efficacy of the CAR T-cell therapy lisocabtagene maraleucel (Breyanzi; liso-cel) in patients with CLL/SLL who experienced disease progression on both a BTK inhibitor and a venetoclax (Venclexta)–based regimen.

Findings from the primary analysis of this study were previously reported and demonstrated rapid and deep responses with the agent at a median follow-up of 21.1 months (range 0.4-55.6). These data supported the FDA's decision to grant priority review to the supplemental biologics license application seeking the expanded indication of liso-cel to include patients with CLL and SLL who had prior exposure to a BTK inhibitor and a BCL2 inhibitor.

A longer median follow-up analysis was conducted in the primary efficacy analysis set, Feldman begins. This population featured a subset of patients who had experienced disease progression following treatment with a BTK inhibitor and BCL2 inhibitor and received liso-cel at a target dose of 100 x 106 CAR+ T cells. At a median follow-up of 23.5 months (range, 0.4-59.6), patients experienced a complete response rate of 20% (95% CI, 10.0%-33.7%) with liso-cel, Feldman reports.

Additionally, the agent elicited sustained undetectable minimal residual disease rates in both blood (64%; 95% CI,45.2%-77.1%) and bone marrow (60%; 95% CI,45.2%-73.6%), she states. The overall response rate with the agent was 44% (95% CI, 30.0%-58.7%), and the median duration of response was 35.3 months (range, 11.01-not reached), Feldman adds. A signal for overall survival benefit was also observed, although further data are needed to confirm this finding, Feldman notes.

Regarding safety, the study reported manageable adverse effects with liso-cel, Feldman continues. There was an 85% incidence of any-grade cytokine release syndrome (CRS) and a 45% incidence of non-CRS neurological events. Importantly, most of these events were low grade, indicating the agent’s favorable safety profile, she says.

Overall, results show that liso-cel may serve as a valuable addition to the treatment armamentarium for this patient subset, and investigators anticipate the agent's expanded approval in both CLL and SLL, Feldman concludes.