Clinical Impact of Pretransplant Blinatumomab in Predominantly Hispanic Adults with B-Cell Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

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Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a potentially curative treatment. Blinatumomab, a bispecific T-cell engager targeting CD19, has shown promise in improving B-ALL outcomes. Our aim is to evaluate the clinical impact of pretransplant blinatumomab. Methods This is a retrospective study includes 145 B-ALL adults who received allogeneic HSCT at Norris Comprehensive Cancer Center from 2014 to 2024. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were evaluated using competing risk regression. Overall survival (OS) and disease-free survival (DFS) were analyzed with Cox proportional hazards model. Results Our cohort was predominantly male (n=85, 58.6%), Hispanic (n =111, 76.6%) with a median age of 42 years (range 20-69) and underwent a pediatric-based regimen (USC ALL 61.1%, Hyper-CVAD 20.8%). Most were Philadelphia (Ph) neg (Ph-negative 40.4%, Ph-positive 35.3%, Ph-like 24.8%) and had unfavorable (51.4%) or intermediate (40.0%) risk cytogenetics (CALGB criteria). Patients most often received haploidentical (haplo) HSCT (haplo 36.4%, MSD 32.9%, MUD 25.9%, MMUD 4.9%) with myeloablative conditioning (93.6%) while in CR1 (68.3%) and achieved measurable residual disease (MRD) negativity (89.7%). Within six months pretransplant, 36 patients (24.8%) received blinatumomab (cycles median 2, range 1-5) for MRD (75.0%) or relapse/refractory disease (25.0%). When comparing patients by pretransplant blinatumomab, age, sex, cytogenetics, induction regimen, donor type, stage, MRD status, and transplant risk index (TRI) did not differ between groups. The blinatumomab group were more often Ph-like (38.9% v. 20.2%; p=0.041). Patients who received blinatumomab had improved DFS (HR 0.24, 95%CI 0.07-0.76, p=0.016) and CIR (HR 0.22, 95%CI 0.05-092, p=0.038), but similar OS (p=0.16) and NRM (p=0.31). Relative to CR1, patients transplant in CR2/3 had worse OS(HR 3.47, 95% CI 1.43=8.42, p=0.006), DFS(HR 2.19, 95% CI 1.16-4.15, p=0.016) and CIR(HR 2.26, 95% CI 1.09-4.67, p=0.028), while pretransplant MRD positivity predicted worse OS(HR 3.63, 95% CI 1.32-10.0, p=0.013) and DFS (HR 2.35, 95% CI 1.04-5.34, p=0.041) on univariate analysis. When controlling for disease status and MRD status at transplant, the blinatumomab group continued to have improved CIR (HR 0.22, 95% CI 0.05-0.92, p=0.039) and DFS (HR 0.24, 95% CI 0.07-0.80, p=0.019) on multivariate analysis. Subgroup analysis of Hispanic patients demonstrated improved DFS with blinatumomab (HR 0.22, 95% CI 0.05-0.94, p=0.041). Conclusion This study demonstrates that pretransplant blinatumomab in adult B-ALL patients undergoing allogeneic HSCT is associated with improved DFS and reduced CIR. These findings suggest incorporating blinatumomab into pretransplant treatment strategies may enhance outcomes for adult B-ALL patients undergoing allogeneic HSCT.

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