Real-World (RW) Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) By High-Risk Features and Prior Treatments: Updated Evidence from the CIBMTR® Registry
Year: 2024
Type: conference-abstract
Abstract: Introduction: Brexu-cel is an autologous anti-CD19 CAR T-cell therapy approved for adults with R/R B-ALL and demonstrated a high complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate (74%) and median overall survival (OS; 25.6 mo; N=78) with >4 y follow-up (FU) in ZUMA-3 (Oluwole et al. ASCO 2024). In a RW study of brexu-cel in pts with R/R B-ALL in the CIBMTR registry (N=150; median FU 6.1 mo), CR/CRi and 6-mo OS rates were both 79%, with safety outcomes consistent with ZUMA-3 (Bezerra et al. ASH 2023). Here, we report updated RW outcomes with longer FU and more pts with key subgroups described. Methods: Adults with R/R B-ALL treated with commercial brexu-cel from 10/01/2021-12/26/2023 were included from the CIBMTR registry. Key subgroups, including prior treatments, lines of therapy (LOT), pre-infusion MRD status, and high-risk features (e.g., aged ≥55 y, ECOG PS ≥2, >50% pre-infusion bone marrow [BM] blasts, comorbidities, and poor cytogenetic risk score), were examined in univariate and multivariate analyses (MVA) for effectiveness and safety outcomes. Results: A total of 242 pts were included (median FU 7.2 mo); median age 46.8 y (range 18.5-84.3), 8% <26 y, 35% ≥55 y, 29% Hispanic, 8% ECOG PS ≥2, 81% had comorbidities (30% with moderate/severe pulmonary symptoms at infusion, 10% with history of cardiac comorbidity, and 9% with ongoing infection at infusion [despite a boxed warning in the US label instructing not to administer brexu-cel to pts with active infection or inflammatory disorders]), and 11% had >50% pre-infusion BM blasts (70% had ≤5%). Pts were heavily pretreated, with median 3 prior LOT (interquartile range [IQR], 2-4; 62% blinatumomab [blina]; 44% inotuzumab ozogamicin [InO]) and 32% had prior allogeneic stem cell transplantation (alloSCT; median 25 mo alloSCT to infusion). Pre-infusion CR/CRi rate was 39% (24% MRD negative). Median vein-to-vein time was 32 d (IQR, 27-42) and 50% had bridging therapy. CR/CRi rate (95% CI) in evaluable pts (n=239) after brexu-cel was 80% (75-85; 68% [60-76] for 145 pts not in CR/CRi pre-infusion). Estimated 6-mo rates (95% CI; n) of duration of remission (DOR), relapse-free survival (RFS), and OS were 67% (58-74; 192; 66% [51-77] in 99 pts not in CR/CRi pre-infusion), 55% (48-62; 242), and 80% (74-84; 242). Of responders, 29% had subsequent alloSCT (median time to alloSCT, 107.5 d [IQR, 84-157]). In MVA, prior blina, InO, and LOT had no significant effectiveness associations. Prior alloSCT was associated with improved DOR (hazard ratio [HR], 0.22 [95% CI, 0.10-0.49]) and RFS (HR, 0.62 [95% CI, 0.40-0.96]). Ongoing infection at infusion was associated with worse CR/CRi (odds ratio [OR], 0.31 [95% CI, 0.10-0.91]), RFS (HR, 1.80 [95% CI, 1.02-3.19]) and OS (HR, 2.67 [95% CI, 1.40-5.10]). There was increased risk of relapse/death for pts not in CR/CRi pre-infusion (HR, 2.08 [95% CI, 1.25-3.45]) vs pts with CR/CRi pre-infusion who were MRD negative. Rates of any Grade (Gr) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) at 100-d FU were 81% (13% Gr ≥3) and 46% (24% Gr ≥3). Day 30 prolonged thrombocytopenia and neutropenia rates (n=224) were 30% and 34%. Cumulative incidence of infection at 3 mo since infusion was 40%. In MVA, pts with prior alloSCT had higher risk of Gr ≥3 ICANS (OR, 2.25 [95% CI, 1.18-4.27]). Pts with >50% pre-infusion BM blasts had higher risk (OR [95% CI]) of Gr ≥3 CRS (6.39 [2.10-19.47]) and infection (2.14 [1.13-4.05]). Other increased risks (OR) included primary refractory disease with any Gr (8.81) and Gr ≥3 (3.34) CRS; cardiac comorbidity with Gr ≥3 CRS (3.12); aged ≥55 y with any Gr ICANS (4.11); poor cytogenetics with any Gr (1.93) and Gr ≥3 (2.58) ICANS; moderate/severe pulmonary symptoms at infusion with Gr ≥3 ICANS (2.35); not in CR/CRi pre-infusion with prolonged neutropenia (3.78); and 12-24 mo from diagnosis to infusion with prolonged neutropenia (3.32 vs <12 mo) and thrombocytopenia (3.99). Cumulative incidence of non-relapse mortality at 6 mo was 4%. Conclusions: In the RW, brexu-cel demonstrated high effectiveness and a safety profile consistent with ZUMA-3 in a broader R/R B-ALL pt population than ZUMA-3. Effectiveness was consistent across prior treatments and most high-risk features. Age was not detrimental to safety while some high-risk features, like >50% pre-infusion BM blasts, may require closer monitoring for safety risks. KW, EB, and YY contributed equally.
Source: Blood
Authors: Kitsada Wudhikarn, Evandro Bezerra, Yang Yang, Miguel-Angel Perales, Nitin Jain, Usama Gergis, Ahmed Aribi, LaQuisa Hill, Jessica T. Leonard, Forat Lutfi, Soyoung Kim, Matthew Bye, Zhen-Huan Hu, Hai-Lin Wang, Zhong-Cheng Luo, Rubina Siddiqi, Rita Damico Khalid, Jessica Speiser, Marcelo C. Pasquini, Partow Kebriaei, Lori Muffly
Institutions: Chulalongkorn University, The Ohio State University, Thomas Jefferson University, Memorial Sloan Kettering Cancer Center, The University of Texas MD Anderson Cancer Center, City Of Hope National Medical Center, City of Hope, Baylor College of Medicine, Oregon Health & Science University, The University of Kansas Health System, Stanford University
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405038884