“These studies have the potential to be practice changing,” said Kathleen Dorritie, MD, a hematologist/medical oncologist at UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, who is not involved in the trial. “Moving CAR-T therapy earlier in the disease course may improve response rates, and also avoid toxicity that can occur with standard chemotherapy.”
That toxicity can undermine the effectiveness of CAR-T as a later option. After a patient has undergone multiple rounds of chemotherapy, it can be harder to collect enough healthy lymphocytes for the procedure. The structure of the BELINDA trial takes this into account.
“The other very unique aspect to the BELINDA trial is that once patients are enrolled, all patients, regardless of what arm they get randomized to, have lymphocytes collected for potential CAR-T cell therapy,” said Dr Bishop. “If they get randomized to the standard-of-care arm, [and] if the patient should happen to progress, they would have already had lymphocytes collected to generate CAR-T cells — and actually as a participant on the trial they will receive their CAR-T cells as part of the trial.” Collecting those lymphocytes upfront, he said, protects them from exposure to salvage chemotherapy and means they may be healthier and more effective.
BELINDA will eventually enroll an estimated 318 patients, 18 years and older, with aggressive B-cell NHL. The study has already enrolled patients across more than 29 centers worldwide.
While the cost of tisa-cel right now could seem high compared with conventional treatments, if it works for more patients, the upfront expense might mean lower overall costs in the long term.
Considering factors like toxicity and risk of recurrence even after second-line treatment, Dr Bishop said, CAR-T could prove to be the better option. “Right now, we’re seeing with CAR-T if you’re in complete remission at 12 months, there’s less than 10% chance of recurrence,” he said.
Disclosures: Michael Bishop: employment, UnitedHealthcare; honoraria, Celgene; consulting or advisory role, Seattle Genetics; speakers’ bureau, Celgene, Juno Therapeutics, and Novartis. For a full list of disclosures, please refer to the original study.
1. Bishop M, Flinn I, Borchmann P, et al. BELINDA: A phase 3 study evaluating the safety and efficacy of tisagenlecleucel versus standard of care in adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Poster presented at: the 34th Annual Meeting & Preconference Programs of the Society for Immunotherapy of Cancer 2019 Annual Meeting (SITC 2019); November 6–10, 2019; National Harbor, MD. Abstract P.402
2. Oluwole OO, Bishop MR, Gisselbrecht C, et al. ZUMA-7: A phase 3 randomized trial of axicabtagene ciloleucel (Axi-Cel) versus standard-of-care (SOC) therapy in patients with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) [published online June 1, 2018]. J Clin Oncol. 2019;36(15_suppl). doi: 10.1200/JCO.2018.36.15_suppl.TPS7585