Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T-cell therapy that has been approved by the US Food and Drug Administration for the treatment of relapsed or refractory mantle cell lymphoma (R/R MCL) in adults. Historically, patients with R/R MCL with TP53 mutation and/or deletion, or a high Ki-67 proliferation index (PI), have had limited treatment options with poor outcomes. At the 2023 ASH Annual Meeting & Exposition, Swetha Kambhampati, MD, City of Hope National Medical Center, Duarte, California, presented findings from their study on real-world outcomes of brexu-cel treatment in patients with R/R MCL with high-risk features, including deletion of TP53 or 17p, Ki-67 PI, and whether the patients were eligible for the ZUMA-2 trial.

The study included 446 patients from 84 US centers who were prospectively enrolled in the Center for International Blood and Marrow Transplant Research observational database for a post-authorization safety study from July 2020 to December 2020. Patients who had received prior non-transplant cellular therapy, had missing data for analysis, or did not receive follow-up care were excluded from the analysis. The effectiveness outcomes included progression-free survival (PFS), overall survival (OS), relapse/progressive disease (REL/PD), overall response rate (ORR), complete response (CR) rate, and duration of response (DOR). The researchers conducted univariate and multivariate logistic regression analyses, along with using Cox proportional hazard models to identify covariates that impacted treatment outcomes.

Of the patients included in the study, 20% (44/220) had deletion of TP53/17p at diagnosis, and 42% (107/252) had Ki-67 PI ≥ 50% at diagnosis. The former group was less likely to undergo prior autologous hematopoietic cell transplant (11% vs 30%), while the latter group was more likely to receive Bruton’s tyrosine kinase inhibitor (BTKi) (92% vs 81%) and bridging therapy (52% vs 37%). Those with Ki-67 PI ≥ 50% at diagnosis were also less likely to receive bendamustine (47% vs 62%). Patients who had either of these high-risk features tended to have a shorter time from diagnosis to brexu-cel infusion. The number of patients who would not have been eligible for the ZUMA-2 study was 297 (67%). This was primarily due to them having the following characteristics: pulmonary impairment (33%), cardiac impairment (21%), prior malignancy (21%), low platelet count (20%), and no prior BTKi (18%).

The researchers evaluated the effectiveness outcomes of the brexu-cel treatment at 12 months of follow-up. They found that patients without deletion of TP53/17p had a CR rate of 80%, an ORR of 90%, a DOR rate of 65%, a PFS rate of 61%, and an OS rate of 77%. For patients with deletion of TP53/17p, the CR rate was 84%, the ORR was 95%, the DOR was 46%, the PFS was 54%, and the OS was 55%. Those with Ki-67 PI ≥ 50% had a CR rate of 84%, an ORR rate of 93%, a DOR rate of 60%, a PFS rate of 58%, and an OS rate of 77%; while those with Ki-67 PI < 50% had a CR rate of 83%, an ORR rate of 92%, a DOR rate of 69%, a PFS rate of 63%, and an OS rate of 73%. Patients who were eligible for the ZUMA-2 trial had a CR rate of 84%, an ORR rate of 92%, a DOR rate of 73%, a PFS rate of 70%, and an OS rate of 82%. Those who were ineligible for the trial had a CR rate of 79%, an ORR rate of 90%, a DOR rate of 60%, a PFS rate of 57%, and an OS rate of 71%. In addition, grade ≥ 3 cytokine release syndrome occurred more frequently in patients who were ineligible for the ZUMA-2- trial vs those who were eligible (13% vs 7%).

The authors found that there appeared to be an association with the deletion of TP53/17p and decreased OS (hazard ratio [HR] 1.79 [95% CI 0.99−3.25]). Deleted TP53/17p was also associated with more frequent prolonged neutropenia (OR 2.85 [1.30−6.27]) and prolonged thrombocytopenia (OR 2.18 [1.04−4.57]). However, these did not impact infections that already required treatment (HR 1.22 [0.79−1.90]) nor the rate of non-relapse mortality among the patients (HR 2.00 [0.77−5.21]).

“These real-world findings with 12 months of follow-up suggest that outcomes of brexu-cel treatment are largely consistent, including a high CR rate, regardless of ZUMA-2 eligibility or the high-risk feature subgroups analyzed,” said Dr Kambhampati and colleagues. The authors note that although patients  without deletion of TP53/17p appear to have longer OS than those with the deletion, the study’s results further support brexu-cel as the standard of care across pts with R/R MCL, including those with high-risk features.

Source: Kambhampati S, Ahmed N, Hamadani M, et al. Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) mantle cell lymphoma (MCL): a CIBMTR subgroup analysis of high-risk characteristics. Presented at: 2023 ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA, and virtual; Abstract 107.