Dr Goy on the Rationale for Launching the ZUMA-18 Trial in Relapsed/Refractory MCL

Andre Goy, MD, physician in chief, Hackensack Meridian Health Oncology Care Transformation Services, chairman, chief physician officer, chief, Lymphoma Division, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale for investigating brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with relapsed/refractory mantle cell lymphoma (MCL) enrolled in the phase 2 ZUMA-2 trial (NCT02601313) and the expanded access ZUMA-18 study (NCT04162756).

Notably, the CAR T-cell therapy brexu-cel was granted approval by the FDA for use in the United States in adult patients with relapsed/refractory MCL in July 2020. This regulatory decision was supported by findings from ZUMA-2. After a median follow-up of 4 years, brexu-cel demonstrated sustained survival benefits in this patient population, evidenced by the median overall survival of 58.7 months among patients who achieved a complete response.

Goy begins by saying that patients diagnosed with MCL typically face relapse despite responding to initial induction therapy. The standard of care predominantly revolves around BTK inhibitors, and when patients progress on chemotherapy, immunotherapy, and BTK inhibitors, their median OS decreases to an approximate range of 3 to 12 months, he explains. Based on this information, there exists an unmet need in this patient population, Goy adds. However, the advent of brexu-cel has revolutionized the MCL treatment paradigm, he elucidates.

Following the closure of the treatment-confirming ZUMA-2 trial in early 2019, patients awaiting commercial availability of brexu-cel lacked access to this therapy Goy expands. To address this gap, the ZUMA-18 study was initiated, catering to a population of patients who would have been ineligible for ZUMA-2 trial due to factors such as advanced age and comorbidities, he says. ZUMA-18 employed a similar study design to ZUMA-2, requiring patients to have progressed on at least 1 prior therapy for MCL, although many patients who enrolled in the ZUMA-18 trial had undergone multiple lines of treatment, Goy states.

Patients were excluded from ZUMA-18 if they had received prior autologous stem cell transplant or if they had disease with central nervous system involvement, he concludes.