Brexucabtagene Autoleucel Yields Durable Long-term Responses in MCL: 3-Year Follow-up From ZUMA-2

Brexucabtagene autoleucel (KTE-X19), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, induced durable long-term responses with manageable safety in patients with relapsed/refractory mantle cell lymphoma (MCL), according to a 3-year follow-up analysis of the ZUMA-2 study.

The ZUMA-2 study is a pivotal, single-arm, multicenter, phase 2 trial exploring KTE-X19 in patients with heavily pretreated MCL that is relapsed/refractory to 1 to 5 prior therapies, including a Bruton’s tyrosine kinase (BTK) inhibitor. The primary end point of the study was objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), OS, adverse event (AE) incidence, blood CAR T-cell levels, and serum cytokine levels.

With a median follow-up of 12.3 months, the primary efficacy analysis demonstrated an ORR of 93%, including a 67% complete response (CR) rate. On the basis of these results, KTE-X19 was approved in the United States and Europe for the treatment of adults with relapsed/refractory MCL.

This follow-up analysis reports outcomes after 3 years of follow-up, including for subgroups by prior therapy (bendamustine and BTK inhibitors) or high-risk characteristics. 

After a median follow-up of 35.6 months, the ORR among all 68 treated patients was 91% (95% confidence interval [CI], 81.8 to 96.7) with 68% complete responses (95% CI, 55.2 to 78.5). The median was 28.2 months (95% CI, 13.5 to 47.1), median PFS was 25.8 months (95% CI, 9.6 to 47.6), and median OS was 46.6 months (95% CI, 24.9 to not estimable).

Post hoc analyses revealed ORR and ongoing response rates were consistent among prespecified subgroups by prior BTK inhibitor exposure or high-risk characteristics.

In an exploratory analysis, patients with prior bendamustine benefited from KTE-X19, but showed a trend toward attenuated T-cell functionality, with more impact of bendamustine given within 6 vs 12 months of leukapheresis.

Late-onset toxicities were infrequent; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period.

“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,” the study authors concluded, “Collectively, these findings confirm the durable benefits of KTE-X19 and support future investigations of CD19-directed CAR T-cell therapy in patients with high-risk MCL in earlier treatment lines,” they added.

Source:

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. Published online June 4, 2022. doi:10.1200/jco.21.02370