Brexucabtagene autoleucel (Brexucel) as a consolidation therapy in B-cell acute lymphoblastic leukemia (B-ALL) post HCVAD/minihcvd-inotuzumab-blinatumomab regimens: Initial Results of a prospective Phase 2 trial.

作者：Jayastu Senapati, Elias Joseph Jabbour, Nitin Jain, Kelly Sharon Chien, Musa E. Yilmaz, Fadi G. Haddad, Guillermo Montalban Bravo, Eitan Kugler, Wei‐Ying Jen, Rita B. Khouri, Maro N. Ohanian, Rebecca E. Garris, Min Zhao, Guillermo Garcia‐Manero, Nicholas James Short, Hagop Kantarjian · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1573 · 被引用次数：4 · 研究领域：CAR-T cell therapy research、Acute Lymphoblastic Leukemia research、Health, Education, and Cultural Studies

Abstract Introduction CD19-directed chimeric antigen receptor T-cell therapy (CAR T) has significantly improved outcomes in relapsed/refractory (R/R) B-ALL. In registrational and real-world studies, patients (pts) with low disease burden had better outcomes and lesser CAR T related toxicity. We hypothesize that the administration of brexucel as consolidation therapy in frontline (FL) high-risk (HR) B-ALL or R/R B-ALL after cytoreduction could be more tolerable and lead to better outcomes and might eventually replace allogeneic stem cell transplantation (ASCT). Methods We conducted a phase 2 clinical trial (NCT06287229) that included pts (³18 years) with FL HR B-ALL, defined by adverse genomics (KMT2A rearrangement [r], complex karyotype [CK] as per NCCN 2022, low hypoploidy/tetraploidy, CRLF2r, TP53 mutation) or persistent/recurrent MRD [MRD+ve] by flow cytometry [FCM] and/or next generation sequencing [NGS] at a LOD of at least 1 in 10-6; or R/R B-ALL. Pts with FL disease received 1-2 cycles of HCVAD or Mini-HCVD-inotuzumab (InO)-blinatumomab (blina) followed by leukapheresis and be in morphological remission. Leukapheresis could be followed by further chemo-immunotherapy and then standard lymphodepletion (LD) with fludarabine-cyclophosphamide before brexucel infusion. Pts in R/R cohort were to receive Mini-HCVD-ino-blina followed by leukapheresis and LD with/without further intervening chemoimmunotherapy. Pts in FL-MRD+ve cohort could proceed directly to leukapheresis. Prim...