In a recent study (Dutch Childhood Oncology Group [DCOG] ALL11) reported in the Journal of Clinical Oncology, Pieters et al found that modifications in therapy appeared to improve outcomes and reduce drug exposure in pediatric patients with acute lymphoblastic leukemia (ALL) compared with treatment in the prior DCOG ALL10 study.
Study Details
As stated by the investigators: “The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three [measurable] residual disease–defined risk groups: standard risk, medium risk, and high risk. IKZF1-deleted ALL in the largest medium-risk group still showed poor outcome…, accounting for a high number of overall relapses. ALL10 showed high toxicity in [patients with] Down syndrome and excellent outcome in ETV6::RUNX1-rearranged ALL. Poor prednisone responders were treated as high risk in ALL10.”
They continued: “In ALL11, maintenance therapy for [IKZF1-deleted ALL] was prolonged from 2 to 3 years. Reductions in treatment were made for [patients with Down syndrome] (omission of anthracyclines), for ETV6::RUNX1 intensification, and for poor prednisone responders (treated as medium risk).”
Key Findings
Among 819 patients aged 1 to 18 years enrolled in ALL11, the rates of 5-year overall survival, event-free survival, cumulative risk of relapse, and cumulative incidence of death in complete remission were 94.2%, 89.0%, 8.2%, and 2.3%, respectively. The respective rates in ALL10 were 91.9%, 87.0%, 8.4%, and 2.9%.
Compared with ALL10, the prolonged maintenance for IKZF1-deleted disease in medium-risk patients enrolled in ALL11 improved the 5-year cumulative risk of relapse from 23.4% to 10.8% (P = .035), event-free survival from 72.3% to 87.1% (P = .019), and overall survival from 83.0% to 92.9% (P = .078). In a landmark analysis 2 years after diagnosis, respective improvements were from 25.6% to 8.8% for the cumulative risk of relapse (P = .008), 74.4% to 91.2% for event-free survival (P = .007), and 88.6% to 95.5% for overall survival (P = .14).
Reductions in therapy in ALL11 vs ALL10 did not worsen the 5-year outcomes in patients with Down syndrome (event-free survival = 87.0%, overall survival = 87.0% in ALL11), poor prednisone responders (event-free survival = 81% vs 73%, overall survival = 94.9% vs 81%), or patients with ETV6::RUNX1-rearrangement (event-free survival = 98.3% vs 95.2%, overall survival = 99.4% vs 98.2%).
The investigators concluded: “Children with IKZF1-deleted ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, Down syndrome, [and those with a poor response to treatment with prednisone]. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.”
Rob Pieters, MD, MSc, PhD, of Princess Máxima Center for Pediatric Oncology, Utrecht, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
