Low- vs standard-dose chemotherapy induction in pediatric AML-M2

A retrospective secondary analysis of the multicenter, randomized, non-inferiority phase III CALS III-AML18 trial (ChiCTR1800015883) evaluated the efficacy and safety of low-dose chemotherapy (LDC) vs standard-dose chemotherapy (SDC) induction in 221 pediatric patients (aged <18 years) with M2 acute myeloid leukemia (AML-M2). The primary outcome was the complete remission (CR) and CR with incomplete recovery (CRi) rate after Induction 1 and 2. Results were published in Cancer Medicine by Ou et al.

Key data: CR/CRi rates were 67.0% with LDC (n = 109) vs 70.5% with SDC (n = 112; p = 0.568) after Induction 1 and 84.4% vs 89.3% (p = 0.740), respectively, after Induction 2. With a median follow-up of 3.44 years, 3-year overall survival (OS; p = 0.304), 3-year relapse-free survival (RFS; p = 0.205), and 3-year event-free survival (EFS; p = 0.218) were similar with LDC vs SDC. Among patients with KIT mutations (LDC, n = 34; SDC, n = 49), the LDC group had lower 3-year OS (p = 0.011), RFS (p = 0.038), and EFS (p = 0.002) vs the SDC group. Among patients who developed sepsis, Grade 3–5 events were less frequent with LDC vs SDC (p < 0.001). The LDC group had shorter neutrophil and platelet recovery times, lower transfusion requirements, and reduced treatment costs during induction than the SDC group.

Key learning: This analysis demonstrated no significant differences in remission or survival outcomes between LDC vs SDC treatment in pediatric patients with AML-M2. LDC was associated with a lower treatment burden, supporting its further evaluation as a toxicity-sparing induction strategy in this population. However, the poorer survival outcomes observed with LDC among patients with KIT mutations suggest molecular features should be considered when evaluating potential low-dose strategies.