In the longest follow-up study of chimeric antigen receptor (CAR) T-cell therapy in patients with mantle cell lymphoma (MCL) to date, brexucabtagene autoleucel induced durable long-term responses and demonstrated a manageable safety profile in patients with relapsed/refractory MCL, according to research published in the Journal of Clinical Oncology.
Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR-T therapy approved for the treatment of relapsed/refractory MCL. The findings from this report come from 3 years of follow up of patients with relapsed/refractory MCL who received KTE-X19 in the pivotal ZUMA-2 study (ClinicalTrials.gov Identifier: NCT02601313).
Patients with relapsed/refractory MCL received a single infusion of KTE-X19 (2 × 106 CAR T cells/kg). The primary endpoint was objective response rate (ORR); partial response (PR), or complete response (CR) as assessed by independent radiologic review committee according to Lugano classification. Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AE). Minimal residual disease (MRD; sensitivity, 1 in 105 cells) was measured as an exploratory endpoint. The investigators evaluated subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor) or high-risk characteristics.
A total of 68 patients received KTE-X19. At data cutoff (July 24, 2021), the median follow-up duration was 35.6 months (range, 25.9-56.3). The investigators reported an ORR of 91% (95% CI, 81.8-96.7), including a CR rate of 68% (95% CI, 55.2-78.5). They reported a median DOR of 28.2 months (95% CI, 13.5-47.1), PFS of 25.8 months (95% CI, 9.6-47.6), and OS of 46.6 months (95% CI, 24.9 to not estimable). The team found the ORR and ongoing response rates were consistent among the prespecified subgroups.
Of 19 patients who were assessed for MRD at month 6, the investigators found 15 (79%) were MRD-negative and had an ORR of 100%. Among the 4 MRD-positive
patients (21%), they reported 2 CRs, 1 PR, and 1 case of progressive disease. At data cutoff, the MRD-positive group had a median DOR 6.1 months, PFS of 7.1 months, and OS of 27 months; the medians for these outcomes were not reached in the MRD-negative group.
The investigators reported no new safety signals and infrequent late-onset toxicities, with only 3% of treatment-emergent AEs of interest in the study occurring since the previous data cutoff.
“In summary, these longer-term ZUMA-2 data demonstrate that a single infusion of KTE-X19 resulted in high rates of durable responses in relapsed/refractory MCL across patients with high-risk disease characteristics, with manageable long-term safety,” concluded the investigators.
Disclosure: This research was supported by Kite, A Gilead Company. Please see the original reference for a full list of disclosures.
Wang M, Munoz J, Goy A, et al. Three-year follow-up of KTE-X19 in patients with relapsed/refractory mantle cell lymphoma, including high-risk subgroups, in the ZUMA-2 study. J Clin Oncol. 2023;41(3):555-567. doi:10.1200/JCO.21.02370