Brexu-Cel Shows Efficacy in Mantle Cell Lymphoma in Real-World Setting
High response rates were seen in patients that would not meet ZUMA-2 eligibility criteria.
Brexucabtagene autoleucel (brexu-cel, Tecartus; Kite), a chimeric antigen receptor (CAR) T-cell therapy, has shown favorable efficacy and safety for the treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) in clinical practice, according to results from a real-world experience study.
These real-world findings were presented at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, held both virtually and in Chicago, Illinoisby Preetesh Jain, MD, assistant professor, lymphoma and myeloma, University of Texas MD Anderson Cancer Center.
"Brexu-cel is an FDA approved therapy for R/R MCL, based on results from ZUMA-2 study. We report the safety and efficacy of BA in standard of care practice among centers in the US Lymphoma CAR-T Consortium,” Jain and colleagues wrote.
This retrospective study collected data from 16 centers part of the CAR T Consortium and included 189 patients who underwent leukapheresis by 12/31/2021 with an intent to manufacture brexu-cel. Investigators collected data including baseline clinical characteristics, bridging therapy, adverse events (AEs) after infusion, and outcome data. These data were used retrospectively to determine ZUMA-2 eligibility (NCT02601313).
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Of patients that underwent leukapharesis, 167 (88%) were infused with brexu-cel and 22 (12%) were not. Patients had a median age of 67 years and patient characteristics included high risk simplified Mantle Cell International Prognostic Index (MIPI) scores (16%), at least 50% Ki-67 index (57%), aggressive histology (41%), TP53 alteration (49%), progression of disease within 24 months (POD24; 51%), and central nervous system (CNS) involvement (10%).
Patients had a median of 3 prior lines of therapy (range, 1-10) and most patients (86%) had received prior BTK inhibitor (BTKi) treatment and had refractory disease to this treatment (89%). Most patients (n = 113; 68%) received bridging therapy including BTKi, venetoclax, and chemotherapy. The median time from leukapheresis to lymphodepletion chemotherapy was 28 days (range, 17-140). ZUMA-2 eligibility criteria would have excluded most patients (n = 130; 78%).
Almost all patients (90%) across centers experienced cytokine release syndrome (CRS) but only 8% of cases were at least grade 3, although 1 case was grade 5. Similarly, the rate of immune effector cell-associated neurotoxicity syndrome (ICANS) was 61% with 32% of cases at grade 3 or higher. These AEs were managed with tocilizumab (n = 125; 76%), corticosteroids (n = 112; 68%), and anakinra (n = 27; 16%). Some patients required ICU admission (n = 32; 20%), vasopressors (n = 18; 11%), and/or mechanical ventilation (n = 5; 3%).
Jain and colleagues analyzed survival outcomes with the Kaplan-Meier method and found that overall response rate (ORR) was 89% and complete response (CR) rate was 70% at day 30, when 155 patients were evaluable. The best ORR was 89%, with an 80% CR rate and 9% partial response (PR) rate.
By subgroup, patients with aggressive histology had an 88% ORR and 79% CR rate; patients with high Ki-67 had an 89% ORR and 77% CR rate; patients with altered TP53 had a 90% ORR and 72% CR rate; patients with CNS involvement had an 81% ORR and 75% CR rate; patients with prior BTKi treatment had an 89% ORR and 79% CR rate; patients that were BTKi-naïve had a 91% ORR and 83% CR rate; and patients that did not meet ZUMA-2 eligibility criteria had an 89% ORR and 78% CR rate.
Median duration of response (DOR) was not reached; DOR at 6 months was 67% (95% CI, 57-75). Median follow-up was 5.6 months (range, 0.2-15.3), median progression-free (PFS) survival was not reached, and PFS at 6 months was 63% (95% CI, 54-71). Median overall survival (OS) was 15.3 months and OS at 6 months was 85% (95% CI, 77-90).
“This multicenter retrospective study demonstrated encouraging safety and efficacy data of BA in R/R MCL in the real-world practice. Despite 78% of the pts being ineligible for ZUMA-2, the responses, CRS, ICANS and outcomes were comparable to ZUMA-2 data. Long term safety and efficacy will be reported,” Jain and colleagues concluded.
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