Predictors of survival in adults with R/R B-ALL treated with blinatumomab and/or inotuzumab ozogamicin

Results from a retrospective, single-center study evaluating predictors of survival in 172 adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) who achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) following first salvage therapy with blinatumomab and/or inotuzumab ozogamicin (InO) were published in Leukemia by Azevedo et al. 

Key data: In multivariate analysis, early relapse (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.23–3.96; p = 0.007) and measurable residual disease (MRD) positivity by multiparameter flow cytometry (MFC) after Cycle 1 of salvage therapy (HR, 3.06; 95% CI, 1.75–5.33; p < 0.001) were independently associated with inferior relapse-free survival (RFS). Early relapse (HR, 2.31; 95% CI, 1.28–4.16; p = 0.005), MFC MRD positivity (HR, 2.21; 95% CI, 1.28–3.81; p = 0.004), and older age (HR, 1.02; 95% CI, 1.00–1.04, p = 0.02) were associated with worse overall survival (OS) outcomes. Patients with MRD negativity after Cycle 1 and either late relapse or primary refractory disease had a 4-year RFS of 54% and a 4-year OS of 66% and were subsequently classified as “lower-risk”. In contrast, patients with MRD positivity after Cycle 1 and/or early relapse had a 4-year RFS of 26% and 4-year OS of 33% and were classified as “higher-risk”. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved RFS among higher-risk patients (4-year RFS, 56% vs 22%; p = 0.03) but not lower-risk patients (4-year RFS, 60% vs 63%; p = 0.82) compared with those who did not receive allo-HSCT. 

Key learning: In this study, MFC MRD status after Cycle 1 of salvage therapy and time to relapse were identified as determinants of OS and RFS in patients with R/R B-ALL, supporting their potential use for risk stratification and identification of patients who may have different outcomes with or without consolidative allo-HSCT.