A Potential New Standard of Care for High-Risk Acute Promyelocytic Leukemia

Chemotherapy-free induction therapy with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) is the standard of care for standard-risk acute promyelocytic leukemia (APML; white blood cell [WBC] count, ≤10×10⁹/L at diagnosis), conferring higher cure rates and lower risk for early mortality from disease-related coagulopathy. High-risk patients have WBC count >10×10⁹/L and greater likelihood of relapse and early mortality despite more-intensive chemotherapy plus ATRA. In a phase 3 industry-supported trial, Platzbecker et al. assessed induction with ATRA–ATO and 2 doses of idarubicin in the first cycle followed by consolidation with 4 cycles of ATRA–ATO, versus induction with ATRA plus 4 doses of idarubicin followed by 3 cycles of consolidation with ATRA plus chemotherapy and 2 years of oral maintenance chemotherapy plus ATRA.

Study enrollment closed early due to slow accrual (related to the COVID-19 pandemic), with 133 participants. At a median follow-up of 37 months, 2-year event-free survival (the primary endpoint) was 88% in the ATRA–ATO arm and 71% in the ATRA–chemotherapy arm. Differentiation syndrome during induction and molecular relapse also were both significantly less likely with ATRA–ATO, although overall survival was similar across all participants due to effective salvage therapies.