PETHEMA LAL-2019: Genetics and MRD for therapy allocation in Ph− ALL

Results from the prospective, multicenter PETHEMA LAL-2019 (NCT04179929) study, evaluating combined centralized genetics and measurable residual disease (MRD) for post-induction therapy allocation in adults (aged 18–60 years) with B-cell precursor (BCP) Philadelphia chromosome–negative (Ph−) acute lymphoblastic leukemia (ALL) and T-cell ALL, were published in Blood by Ribera et al. Patients with high genetic risk (HGR), those who required two induction cycles to reach complete remission (CR), patients with CR and measurable residual disease (MRD) ≥0.01% at end-of-induction (EoI)-1, MRD ≥0.001% at the end of early consolidation/reinduction, and any patient with early T-ALL (ETP-ALL) were assigned to allogeneic hematopoietic stem cell transplantation (allo-HSCT; n = 243), while remaining patients were assigned to chemotherapy (n = 157). The primary objective was overall survival (OS). Secondary objectives included CR and MRD response rates, event-free survival (EFS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR).

Key data: At a median follow-up of 2.0 years, the 3-year OS probability was 64% (95% confidence interval [CI], 58–69%). The 3-year OS rate was significantly higher among patients assigned to chemotherapy compared with allo-HSCT (81% vs 54%; p < 0.001). The CIR was higher among patients assigned to allo-HSCT vs chemotherapy (46% vs 30%; p = 0.003). Patients with EoI MRD <0.01% without HGR (n = 109) achieved 3-year OS of 81% (95% CI, 70–89%) vs 50% (95% CI, 34–63%) for patients with EOI MRD <0.01% with HGR (n = 64; p < 0.001). 

Key learning: Combining centrally assessed baseline genetics with early MRD response enables accurate post-remission treatment allocation in adults with Ph− ALL, confirming the independent prognostic significance of HGR, particularly in BCP-ALL.