Brexu-Cel Demonstrates Continued Durable Responses at 3-Year Follow-Up in ZUMA-2 Study for Relapsed/Refractory MCL

The 3-year follow-up update from the phase 2 ZUMA-2 trial showed continued responses for patients with relapsed/refractory mantle cell lymphoma treated with brexucabtagene autoleucel.

Brexucabtagene autoleucel (Tecartus) continued to demonstrated durable and long-term responses in patients with relapsed/refractory mantle cell lymphoma, according to results from the 3-year follow-up of the phase 2 ZUMA-2 trial (NCT02601313) published in The Journal of Clinical Oncology.

At a median follow-up of 35.6 months, the objective response rate (ORR) was 91.0% (95% CI, 81.8%-96.7%) among the 68 treated patients who were treated, of whom 68.0% (95% CI, 55.2%-78.5%) had a complete response (CR) and 24.0% (95% CI, 14.1%-35.4%) had a partial response (PR). The median duration of response (DOR) was 28.2 months (95% CI, 13.5-47.1), median progression-free survival (PFS) was 25.8 months (95% CI, 9.6-47.6), and median overall survival (OS) was 46.6 months (95% CI, 24.9–not estimable).

As previously reported, total of 74 patients enrolled and underwent leukapheresis, 68 of whom received full treatment. In the updated analysis, after initial stable disease or PR, 25 patients converted to a CR, with the median time to response conversion of 2.3 months. At data cut-off, the median DOR was 46.7 months for patients who had a CR (n = 46) and 2.2 months for patients with a PR (n = 16). Of the first 28 patients treated, the median follow-up was 51.1 months; the median DOR was 36.5 months in 26 responders and 29% had an ongoing response.

For patients whose best response was CR, the median PFS was 48.0 months. For those with a PR the median PFS was 3.1 months and 2.3 months with no response. At the post-infusion week 4 visit, 94% of patients achieved a response, which was followed by a landmark analysis assessing PFS by response type. The median PFS for those whose best response was a CR was 46.7 months, 13.6 months for a PR, and 11.0 months with no response. The cumulative incidence of relapse during follow-up confirmed patients who had CR as a best response were less likely to relapse than those with PR or no response (P <.0001).

The median OS in patients whose best response was a CR was not reached, and was 16.3 months for PR and 8.5 months for no response. Minimal residual disease (MRD) was assessing in 19 patients at 6 months, of whom 79% were MRD-negative with an ORR of 100%. Of those who were MRD-positive, 2 achieved a CR, 1 achieved a PR, and 1 had progressive disease. Additionally, in the MRD-positive population, the median DOR was 6.1 months, median PFS was 7.1 months, and median OS was 27.0 months. For those who were MRD-negative, the median DOR, PFS, and OS were not reached at data cut-off, and 60% had an ongoing response.

Of those in the intent-to-treat population, the ORR was 84.0% (95% CI, 73.4%-91.3%), including a 62.0% (95% CI, 50.1%-73.2%) CR rate and a 22.0% (95% CI, 12.9%-32.7%) PR rate. The median PFS was 24.0 months and the 24-month PFS rate was 49.0%. Moreover, the median OS in this population was 47.4 months, with a 24-month OS rate of 56.0%.

Investigators did not observe any new safety signals during longer follow-up, with 3% of all treatment-emergent adverse effects (AEs) occurring since the previous data report. The most frequent grade 3 or higher AEs was neutropenia with 1% of patients having grade 3 and 10% having grade 4 events. Grade 3 or higher serious AEs were reported in 10% of patients, with 1 patient having grade 3 encephalopathy that was not related to treatment. Two patients had serious AEs related to treatment, including 1 with grade 3 pneumonia and grade 3 upper respiratory tract infection, and 1 with grade 3 influenza.

A total of 3 patients experienced fatal AEs which included salmonella bacteremia beginning at 24.9 months, myelodysplastic syndrome occurring at 25.2 months, and acute myeloid leukemia occurring at 37.5 months.

Reference

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