Clinical outcomes with brexucabtagene autoleucel in refractory mantle cell lymphoma: A systematic review and single-arm meta-analysis with contextual comparison to lisocabtagene maraleucel.

Abstract

e19010 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has improved outcomes for patients with refractory mantle cell lymphoma (MCL). Two CD19-directed CAR-T products, brexucabtagene autoleucel (brexu-cel) and lisocabtagene maraleucel (liso-cel), have demonstrated activity, but no direct comparative trials exist. We conducted a systematic review and single-arm meta-analysis to summarize brexu-cel outcomes and contextualize them with TRANSCEND liso-cel results. Methods: Clinical trials and observational studies of brexu-cel in adults with MCL were identified. Primary outcomes were complete response (CR), progression-free survival (PFS), and grade ≥3 cytokine release syndrome (CRS). Secondary outcomes included overall response rate (ORR), overall survival (OS), duration of response (DOR), and immune effector cell–associated neurotoxicity syndrome (ICANS). Brexu-cel outcomes were pooled using random-effects model; liso-cel outcomes were summarized descriptively. Results: Four brexu-cel studies (n=796) and TRANSCEND liso-cel (n=88) were analyzed. Median age ranged from 65 to 68.5 years. TP53 mutations and central nervous system involvement were more frequent in liso-cel–treated patients, while active CNS disease was excluded in ZUMA-2. For brexu-cel, pooled ORR was 90.2% (95% CI, 88.8–91.5) with CR 81.7% (95% CI, 80.1–83.4). Twelve-month DOR, PFS, and OS were 69.7%, 61.9%, and 76.3%, respectively. In TRANSCEND, liso-cel ORR was 86.5% with CR 74.3%; twelve-month DOR, PFS, and OS were 52.9%, 50.8%, and 61.8%. All-grade CRS occurred in 90.0% of brexu-cel–treated patients (grade ≥3, 9.1%) versus 61.0% (grade ≥3, 1.0%) with liso-cel. All-grade and grade ≥3 ICANS occurred in 61.1% and 29.4% with brexu-cel versus 31.0% and 8.0% with liso-cel. Conclusions: Brexu-cel demonstrated high pooled efficacy in refractory MCL. When contextualized with TRANSCEND, brexu-cel was associated with higher rates of CRS and ICANS compared with liso-cel. Interpretation is limited by cross-trial comparisons and limited real-world data for liso-cel. These findings inform CAR-T selection in refractory MCL in the absence of head-to-head trials. CD19 CAR-T outcomes in refractory MCL. Characteristics/outcomesValues shown as % (95% CI) Liso-cel (TRANSCEND, n=88) Brexu-cel (pooled, n=796)* Age, yTP53 mut, %CNS involvement, % 68.5238 65–6815–480–10 ORR, %CR, % 86.5 (78.1–94.9)74.3 (63.8–84.8) 90.2 (88.8–91.5)81.7 (80.1–83.4) DOR 12 mo, %PFS 12 mo, %OS 12 mo, % 52.9 (40.9–65.0)50.8 (39.6–62.0)61.8 (51.2–72.4) 69.7 (61.5–77.9)61.9 (58.3–65.5)76.3 (73.2–79.4) CRS any, %CRS ≥3, % 61.0 (50.5–71.5)1.0 (–5.8–7.8) 90.0 (88.6–91.3)9.1 (6.8–11.4) ICANS any, %ICANS ≥3, % 31.0 (21.3–40.7)8.0 (2.3–13.7) 61.1 (57.7–64.6)29.4 (26.0–32.9) *ZUMA-2 (n=68); Ahmed (n=476); O’Reilly (n=83); Wang (n=169).