Dr Neelapu on Clinical Trial Data With CAR T-Cell Therapy in Lymphoma

Sattva S. Neelapu, MD, deputy department chair, professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses key clinical trial data that support the use of CAR T-cell therapy in standard practice for patients with lymphoma.

Presently, 4 FDA-approved, CD19-directed CAR T-cell products are available for the treatment of patients with lymphoma, Neelapu begins. Axicabtagene ciloleucel (axi-cel; Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (liso-cel; Breyanzi) were approved for use in third-line lymphoma settings based on findings from the single-arm phase 1 ZUMA-1 (NCT02348216), phase 2 JULIET (NCT02445248), and phase 1 TRANSCEND-NHL-001 (NCT02631044) studies, respectively. These studies revealed notable outcomes, with approximately 40% of patients achieving sustained remissions with CAR T-cell therapy in each, he reports.

Recently, there has been a shift toward evaluating CAR T-cell therapy in the second-line setting through randomized phase 3 trials, he continues. Two of these trials, ZUMA-7 (NCT03391466) and TRANSFORM (NCT03575351), yielded positive results and subsequent second-line FDA approvals for axi-cel and liso-cel, NCT03575351. These regulatory decisionswere based on evidence showcasing improvements in event-free survival and overall survival with the CAR T-cell therapies compared with the existing standard of care (SOC), which typically involved salvage chemotherapy followed by stem cell transplantation, Neelapu elucidates. These pivotal developments have fundamentally altered treatment for patients with large B-cell lymphoma (LBCL), establishing CD19-directed CAR T-cell therapy as the new SOC, he adds.

Furthermore, the phase 2 TRANSCEND-PILOT-017006 study (NCT03483103) investigated liso-cel in the second-line setting in transplant-ineligible patients with non-Hodgkin lymphoma, affirming the efficacy and tolerability of the agent in this patient population. As a result, both transplant-eligible and -ineligible patients with LBCL now have access to CD19-directed CAR T-cell therapy as recommended second-line treatment options, he explains.

In the realm of follicular lymphoma (FL), 2 trials have demonstrated promising efficacy with CAR T-cell therapies in the third-line setting, he expands. These single-arm phase 2 studies exhibited impressive complete response rates ranging from 70% to 80%, as well as noteworthy durability, according to Neelapu. These trials led to FDA approvals for axi-cel in the third-line setting for patients with FL, providing patients with additional treatment options and renewed hope for improved outcomes, he concludes.