Outcomes of children and young adults with B-cell acute lymphoblastic leukemia given blinatumomab as last consolidation treatment before allogeneic hematopoietic stem cell transplantation

Abstract

Blinatumomab has remarkable efficacy in patients with relapsed/refractory (r/r) or measurable residual disease (MRD)-positive B-cell acute lymphoblastic leukemia (B-ALL). In many patients, blinatumomab treatment is followed by allogeneic hematopoietic stem cell transplantation (HSCT). However, the influence of blinatumomab on HSCT outcomes in children and young adults (YA) remains to be fully elucidated. We conducted a single-center, retrospective analysis of patients given blinatumomab as last treatment before HSCT. Seventy-eight pediatric and YA patients were evaluated. With a median follow- up of 23.23 months, the 2-year disease-free (DFS) and overall survival (OS) probability were 72.2% and 89.2%, respectively, with a 2-year cumulative incidence of non-relapse mortality (NRM) of 2.6%. A trend toward improved 2-year DFS, but not OS, was noted in patients transplanted in first complete remission (CR1) (92.9%) compared to those in second or greater remission (CR2/3) (68.5%; P=0.18) due to a lower cumulative incidence of relapse (0% vs. 29.9%; P=0.05). Among CR2/3 patients, those receiving the sequential combination of inotuzumab and blinatumomab had a significantly lower cumulative incidence of relapse as compared to those who did not receive inotuzumab (9.5% vs. 40.4%; P=0.023). Relapse after HSCT occurred in 16 patients, all exhibiting CD19-positive blasts; ten of them received anti-CD19 chimeric antigen receptor T-cell (CAR T) therapy and two inotuzumab as salvage therapy, leading to a 2-year post-relapse OS of 52.7%. Our results indicate that HSCT following blinatumomab in children and YA with B-ALL is highly effective, being associated with low NRM and not affecting the efficacy of subsequent salvage immunotherapies, including CAR T cells.

Figure 1.

Cumulative incidence analyses for relapse and non-relapse mortality in the cohort. (A) Cumulative incidence of relapse (CIR) of the whole cohort. (B) CIR according to disease status at hematopoietic stem cell transplantation (complete remission 1 [CR1, red line] vs. complete remission ≥2 [CR≥2, black line]). (C) CIR according to use of inotuzumab in the induction/consolidation treatment of relapse, CR≥2 patients only (no inotuzumab [black line] vs. inotuzumab [red line]). (D) Cumulative incidence of non-relapse mortality (NRM) of the whole cohort.

Figure 2.

Survival analysis of the cohort. (A) Overall survival (OS) of the whole cohort. (B) Disease-free survival (DFS) of the whole cohort. (C) DFS according to complete remission number at hematopoietic stem cell transplantation (complete remission 1 [CR1, red line] vs. complete remission ≥2 [CR≥2, black line]). (D) DFS according to use of inotuzumab in the induction/consolidation treatment of relapse, CR≥2 patients only (no inotuzumab [black line] vs. inotuzumab [red line]).