Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplant in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia.

BACKGROUND: Blinatumomab, a bispecific T-cell engager that binds CD19 in leukemic cells and CD3 in cytotoxic T-cells and leads to leukemic blast lysis, is often used in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R-B-ALL) prior to allogeneic hematopoietic cell transplant (allo-HCT). Concerns about the potential risk of Blinatumomab-related immune-mediated toxicities after allo-HCT have not been adequately addressed. These include graft-versus-host disease (GVHD), delayed engraftment and graft failure or rejection. Pediatric-specific data reporting post-HCT outcomes of patients treated with Blinatumomab is scarce and limited to small cohorts.

OBJECTIVE: We sought to investigate the clinical outcomes of pediatric patients with R/R-B-ALL who received Blinatumomab therapy pre-HCT, focusing on overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) as well as the incidence of immune-mediated post-HCT complications including GVHD, delayed neutrophil or platelet engraftment, graft failure and rejection. Additionally, we investigated Blinatumomab's effects on B-cell reconstitution via virtue of intravenous immunoglobulin independence achievement post-HCT.

STUDY DESIGN: We conducted a single center, retrospective study including patients with B-ALL receiving Blinatumomab therapy pre-HCT, with allo-HCT occurring between 2016 and 2021 at our institution. Patients receiving Blinatumomab for relapse after allo-HCT were excluded. Patients receiving chemotherapy alone pre-HCT in the same period were included as control group. Seventy-two patients were included, 31 of whom received Blinatumomab pre-HCT. Survival estimates were obtained using the Kaplan-Meier method and the Log-Rank test was used to analyze differences between groups. Categorical variables were compared between groups using Chi Square Test or Fisher's Exact Test, while continuous variables were compared using Wilcoxon Rank Sum Test. Cumulative incidences were estimated using competing risks methods and the Gray's test was used to analyze differences between groups. Cox proportional hazards regression model was used for univariate and multivariable analysis for OS. Landmark analysis was performed at the set time points of 30 and 100 days post-HCT.

RESULTS: Most patients in the study had high-risk, relapsed B-ALL. Blinatumomab therapy induced minimal residual disease (MRD)-negative remissions in all patients, while 5 patients (12.2%) receiving chemotherapy alone had persistent MRD pre-HCT. Time from start of therapy to date of allo-HCT was shorter for patients who received Blinatumomab vs chemotherapy (p<0.0001). Blinatumomab therapy was associated with greater LFS compared to chemotherapy alone (p=0.049), but when limited to one-year, LFS was not found to be significantly different from the control (p=0.066). There appeared to be higher OS, lower CIR and NRM in those receiving Blinatumomab compared to the control group, however, this was not significant. None of the variables assessed in multivariable analysis were associated with differences in OS. When compared to the control group, Blinatumomab therapy did not result in higher incidence of acute or chronic GVHD, delayed neutrophil or platelet engraftment, and graft failure or rejection. Time to IVIG infusion independence post-HCT was similar between groups.

CONCLUSIONS: This study supports the use of Blinatumomab salvage therapy for R/R-B-ALL pre-HCT given its efficacy in inducing MRD- remissions, optimizing LFS and its lack of association with increased incidence of post-HCT adverse immune-mediated toxicities. Larger, prospective studies are needed to confirm these findings and investigate Blinatumomab's effect in long-term post-HCT events.