Dr Kambhampati on the Rationale For Evaluating Real-World Outcomes With Brexu-Cel in MCL

Swetha Kambhampati, MD, hematologist/oncologist, assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the rationale for evaluating outcomes with brexucabtagene autoleucel (Tecartus; brexu-cel) in a subgroup anlaysis of patients with relapsed/refractory mantle cell lymphoma (MCL), and how prior data from the phase 3 ZUMA-2 study (NCT02601313) supported the inception of this trial.

Brexu-cel is currently the only FDA-approved CAR-T product for the treatment of patients with relapsed/refractory MCL, Kambhampati begins. The agent's approval in 2020 was based on findings from the pivotal ZUMA-2 trial, which demonstrated that treatment with brexu-cel produced an overall response rate of 91%, including a complete response rate of 68% in patients who had received more than 2 prior lines of therapy. Notably, all patients enrolled in ZUMA-2 had been previously treated with BTK inhibitors, although the FDA indication for brexu-cel doesn't require patients to have received prior treatments, Kambhampati notes. Moreover, the estimated median duration of response with the agent was not reached after a median follow-up of 8.6 months.

Regarding safety, 18% and 37% of patients treated with brexu-cel experienced grade 3 or greater cytokine release syndrome (CRS) and neurologic toxicities, respectively, Kambhampati details. No grade 5 CRS or neurologic events occurred. The agent was also associated with immune effector cell-associated neurotoxicity syndrome (ICANS) events and certain infections, Kambhampati notes. However, the overall data appeared promising and substantiated the product's approval, she states.

Taking these findings into account, and acknowledging the selective eligibility criteria often present in clinical trials like ZUMA-2, Kambhampati says that the assessment of real-world safety and efficacy outcomes for brexu-cel was deemed necessary. Accordingly, a subgroup analysis was designed to ascertain how these clinical trial findings manifest within a real-world population of patients with relapsed/refractory MCL, Kambhampati says. These patients had progressed on up tp 3 or more prior lines of therapy.

In addition to identifying potential disparities in real-world clinical practice, the study sought to examine the influence of prior treatments, such as bendamustine, BTK inhibitors, autologous stem cell transplant, and the number of prior lines of therapy, on these outcomes, Kambhampati concludes.

Dr Kambhampati had no relationships to disclosure.