Predictors of survival in adults with B-cell acute lymphoblastic leukemia treated with blinatumomab and/or inotuzumab ozogamicin in first salvage

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with B-cell-directed immunotherapies remains controversial. We analyzed 172 adults treated in first salvage with blinatumomab and/or inotuzumab ozogamicin (InO)-based regimens to determine prognostic factors and benefit from allo-HSCT after achieving remission. Relapse within 12 months of initial diagnosis (HR 2.21, 95%CI 1.28-4.16) and measurable residual disease (MRD) positivity by multiparametric flow cytometry after cycle 1 of salvage (HR 3.06, 95%CI 1.75-5.33) predicted inferior relapse-free survival (RFS) on multivariate analysis; both factors as well as older age predicted inferior overall survival (OS). Patients who achieved early flow MRD negativity and had late relapse or were primary refractory to frontline therapy did not benefit from allo-HSCT (4-year RFS 60% vs 63% without allo-HSCT, p = 0.82), while allo-HSCT improved outcomes in patients with MRD positivity and/or relapse within 12 months (4-year RFS 56% vs. 22% without allo-HSCT, p = 0.03). MRD status after cycle 1 of salvage therapy and duration of first remission can risk stratify adults with R/R B-ALL; those with early MRD negativity and late relapse or primary refractory disease may have favorable outcomes without consolidative allo-HSCT.