Long-term follow-up of patients in ZUMA-2 cohorts 1 and 2 showed that 39% of patients with relapsed/refractory mantle cell lymphoma were alive after 5 years; patients in these cohorts received brexucabtagene autoleucel, the only chimeric antigen receptor (CAR) T-cell therapy to have 5-year follow-up data in this patient population. The findings were reported by lead investigator Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, Houston, at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 4388).
ZUMA-2 is an ongoing, single-arm, open-label pivotal study in patients with relapsed or refractory mantle cell lymphoma treated with brexucabtagene autoleucel. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy, and a Bruton’s tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The study enrolled 86 adult patients. The primary endpoint was objective response rate per the Lugano Classification (2014), defined as the combined rate of complete response and partial responses as assessed by an independent radiologic review committee.
In the 5-year analysis, median follow-up for cohorts 1 and 2 was 67.8 months (95% confidence interval [CI] = 58.2–88.6 months) and 72.3 months (95% CI = 70.1–74.3 months), respectively. Median investigator-assessed duration of response and progression-free survival were 36.5 months (95% CI = 17.7–48.9 months; n = 60; with 17 patients in ongoing response, all complete responses) and 25.3 months (95% CI = 12.7–46.6 months; n = 68) in cohort 1; and 57.5 months (95% CI = 4.7 months to not estimable; n = 12; with 3 patients in ongoing response, all complete responses) and 29.5 months (95% CI = 3.3 months to not estimable; n = 14) in cohort 2.
Median overall survival was 46.5 months (95% CI = 24.9–60.2 months) in cohort 1 and not reached (95% CI = 9.4 months to not estimable) in cohort 2. The 60-month overall survival rates were 39% (95% CI = 26.7%–50.1%) in cohort 1 and 54% (95% CI = 23.8%–76.2%) in cohort 2.
No new safety signals were detected, and no secondary T‑cell malignancies were reported at any time in ZUMA-2.
“More than 3 years after its approval, [brexucabtagene autoleucel] continues to deliver in relapsed/refractory mantle cell lymphoma,” said Dr. Wang. “It is encouraging to see these results in a heavily pretreated population and consistency across both cohorts.”
Disclosure: Dr. Wang has received honoraria, served as a consultant, or received research funding from the National Institutes of Health, Scripps, Studio ER Congressi, Amphista Therapeutics, ADC Therapeutics, Pharmacyclics, Nurix, Physicians Education Resources, Merck, MSC National Research Institute of Oncology, PeproMene Oncology, Miltenyi Biomedicine, Oncternal, Lilly, Be Biopharma, PraXel, South African Clinical Hematology Society, WebMD, Deciphera, Genentech, InnoCare, Janssen, Juno Therapeutics, Kite, MJH Life Sciences, Genmab, Dava Oncology, Catamount Medical, CAHON, BMS/Celgene, BioInvent, BeiGene, AstraZeneca, Acerta Pharma, and AbbVie. For full disclosures of the study authors, visit ash.confex.com
