Brexu-cel Yields Consistent Efficacy in R/R Mantle Cell Lymphoma in SOC Setting

Treatment with brexucabtagene autoleucel (Tecartus; brexu-cel) demonstrated consistent safety and efficacy outcomes among patients with relapsed or refractory mantle cell lymphoma comparable to outcomes observed in the phase 2 ZUMA-2 study (NCT02601313), according to a study published in the Journal of Clinical Oncology.

“CAR T-cell therapy with brexu-cel for MCL shows similar performance in the standard-of-care setting compared [with] the ZUMA-2 clinical trial that led to FDA approval [of brexu-cel],” according to an expert from Moffitt Cancer Center.

After a median follow-up of 14.3 months, patients who received brexu-cel infusion had a best objective response rate (ORR) of 90%, including a complete response (CR) rate of 82% of patients and a partial response (PR) of 8%. The 6-month progression-free survival (PFS) rate was 69% (95% CI, 61%-75%) and the 12-month rate is 59% (95% CI, 51%-66%).

“CAR T-cell therapy with brexu-cel for MCL shows similar performance in the standard-of-care setting compared [with] the ZUMA-2 clinical trial that led to FDA approval [of brexu-cel],” author Michael D. Jain, MD, Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, stated in a written comment to CancerNetwork^®.

Investigators of the retrospective study evaluated the efficacy and safety of brexu-cel in relapsed/refractory MCL in standard-of-care practice across 16 United States Lymphoma CAR T Consortium centers.

Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021 to manufacture commercial brexu-cel were included in the study. Investigators retrospectively abstracted baseline clinical and pathologic characteristics at time of leukapheresis and retrospectively identified patient eligibility for the ZUMA-2 trial.

Outcome measures included responses to brexu-cel therapy, time-to-event outcomes, and outcomes based on prognostic subgroups. Investigators also conducted subset analyses including outcomes in Bruton tyrosine kinase (BTK) inhibitor-naïve patients, the potential impact of bridging therapy, and effects of prior bendamustine exposure.

Brexu-cel was successfully manufactured in 96% of cases and infused in 89% of patients who received leukapheresis; this was considered comparable with respective rates observed in the ZUMA-2 trial (96% vs 62%).

Overall, 14% of patients who underwent leukapheresis would have been ineligible for the ZUMA-2 study due to being BTK inhibitor– or bendamustine-naïve, and 65% would have been ineligible based on disease status or clinically significant comorbidities.

The median patient age was 67 years (range, 34-89), and 76% of patients were male. Of note, high-risk prognostic features—including high-risk features by simplified MCL international prognostic index (MIPI)—were present in 21% of patients. Ki-67 expression of 50% or more was present in 58%, blastoid or pleomorphic variant disease in 43%, and TP53 aberrations in 49%.

Complex karyotype was noted in in 29% of patients and disease progression within 24 months of first-line therapy was observed in 51%. Additionally, patients had a median of 3 (range, 1-10) prior lines of therapy and 77% had had progressed following treatment on a BTK inhibitor.

When responses to brexu-cel were assessed based on patient subgroup, investigators reported ORR and CR rates of 72% and 88% for those with TP53 aberrations (P = .029), 65% and 82% for high-risk simplified MIPI (P = .019), and 76% and 89% for disease progression within 24 months of first-line therapy (P = .028), respectively; all subgroups were associated with lower CR rates.

The median overall survival (OS) following brexu-cel infusion was not reached (95% CI, 18.7-not evaluable [NE]). Additionally, the OS rate was 86% (95% CI, 79%-90%) after 6 months and 75% (95% CI, 67%-81%) after 12 months.

Investigators indicated that PFS was shorter for patients with a high-risk simplified MIPI (HR, 3.82; 95% CI, 1.92-7.59; P <.001), Ki-67 of 50% or more (HR, 3.02; 95% CI, 1.43-6.38; P = .007) TP53 aberrations (HR, 1.98; 95% CI, 1.18-3.31; P = .008), complex karyotype (HR, 2.23; 95% CI, 1.25-3.98; P = .005), or blastoid or pleomorphic variant disease (HR, 1.61; 95% CI, 1.03-2.53; P = .036). Additionally, high-risk simplified MIPI, TP53 aberrations, and complex karyotypes were linked with inferior OS.

Investigators reported no statistically significant differences in outcomes between BTK inhibitor–naïve and BTK inhibitor–exposed patients. Additionally, response to bridging therapy did not correlate with statistically significant differences in OS and PFS compared with those who did not receive bridging therapy.

In the intent-to-treat analysis, patients who were exposed to bendamustine had worse PFS regardless of whether they received agent within 6 months (HR, 1.90; 95% CI, 1.11-3.28; P <.0001) or 6 to 24 months (HR, 1.90; 95% CI, 1.10-3.30; P <.001) before undergoing leukapheresis vs those with no exposure. Patients who previously received bendamustine also had inferior OS outcomes (P = .009).

Reference

Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: results from the US Lymphoma CAR T Consortium.J Clin Oncol. Published online February 8, 2023. doi:10.1200/JCO.22.01797