A multicenter phase 3 trial began enrolling patients earlier this year to test the safety and efficacy of tisagenlecleucel (tisa-cel/Kymriah®) as a second-line therapy for aggressive B-cell non-Hodgkin lymphoma (NHL).
Tisa-cel, an anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, has already been approved for use in patients who have relapsed after receiving 2 lines of therapy. But it’s possible that, if administered sooner across treatment regimens, CAR-T could help more patients avoid relapse. The new study on this topic, known as BELINDA, aims to answer that question.
“The hypothesis is that CAR-T cells should improve upon progression-free survival as compared to standard of care,” said Michael Bishop, MD, director of the hematopoietic stem cell transplantation program at the University of Chicago Medicine, Illinois, and one of the BELINDA coauthors. Dr Bishop presented the study protocol at the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer, or SITC 2019, in National Harbor, Maryland.1
Around a third of patients with non-Hodgkin lymphoma (NHL) will relapse after receiving first-line immunochemotherapy, and another 10% to 15% do not respond to initial treatment. For these patients, the outlook is grim: median overall survival is less than 12 months. Second-line treatment consists of high-dose chemotherapy combined with autologous stem cell transplant, but fewer than half of patients will qualify for a transplant. “You’ve got half the patients who won’t get the transplant, and the other half that do, only a quarter of those will have sustained remission,” said Dr Bishop. “It’s a large unmet patient need.”
Dr Bishop went on to explain that previous trials have indicated that some 30% to 40% of patients receiving CAR-T therapy for multiply relapsed or refractory NHL have achieved long-term remission. “The other exciting thing about this trial is it’s moving CAR-T up the treatment algorithm,” he said.
The BELINDA trial is a multicenter, phase 3, open-label trial, in which patients are randomly selected to receive treatment in 1 of 2 arms: tisa-cel, or standard of care. Similar to the ZUMA-7 trial,2 which tested another CAR-T therapy called axicabtagene ciloleucel (Yescarta®), BELINDA is enrolling patients whose disease either does not respond to first-line therapy (rituximab and anthracycline) or has returned within 12 months, and who are eligible for autologous stem cell transplant.