Results of the prospective EORTC Children Leukemia Group study 58081 in precursor B‐ and T‐cell acute lymphoblastic leukemia

Abstract

Abstract Here, we report the results of the prospective cohort study EORTC‐CLG 58081 and compare them to the control arm of the randomized phase 3 trial EORTC‐CLG 58951, on which treatment recommendations were built. In both studies, patients aged 1–18 years with BCR::ABL1 negative acute lymphoblastic leukemia of the B‐lineage (B‐ALL) or T‐lineage (T‐ALL) were treated using a BFM backbone without cranial irradiation. Similarly to the control arm of 58951, prednisolone (PRED) 60 mg/m2/day was used for induction therapy, but a few modifications were made. Dexamethasone (DXM) was used in average‐risk 2 (AR2) T‐ALL and B‐ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high‐dose methotrexate, and a postconsolidation MRD time point was added to stratify patients. Between 2011 and 2017, 835 patients were prospectively enrolled in the 58081 study. Overall, the 5‐year event‐free survival (EFS) was 84.8% versus 83.6% (hazard ratio [HR], 0.96 [95% confidence interval [CI]: 0.76–1.21]) for 58081 versus 58951 considered as a control group, respectively, 84.3% versus 84.9% (HR, 1.06 [99% CI: 0.75–1.49]) in B‐ALL but 87.3% versus 76.6% (HR, 0.59 [99% CI: 0.28–1.24]) in T‐ALL. The comparison between the two studies regarding EFS differed by risk group (p = 0.012). The HR was 2.15 (99% CI: 0.67–6.85) for very low‐risk but 0.34 (99% CI: 0.13–0.89) for AR2. The particularly favorable results observed in the T‐ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.