As reported in the Journal of Clinical Oncology by Platzbecker et al, the European intergroup phase III APOLLO trial showed that an all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO; ATRA-ATO)–based regimen was associated with improved event-free survival vs a standard ATRA plus anthracycline-based chemotherapy (ATRA-CHT) regimen among patients with newly diagnosed high-risk acute promyelocytic leukemia.
Study Details
In the multicenter trial, 133 patients were randomly assigned to receive:
- ATO at 0.15 mg/kg once daily and ATRA at 45 mg/m2 twice daily until complete remission, with two doses of idarubicin at 12 mg/m2 on days 1 and 3, followed by consolidation therapy consisting of four ATRA-ATO cycles (ATRA-ATO group, n = 68)
- Induction with ATRA at 45 mg/m2 twice daily and idarubicin at 12 mg/m2 once daily on days 1, 3, 5, and 7, followed by three cycles of chemotherapy-based consolidation and 2 years of maintenance therapy with ATRA given on days 92 to 106 for six 106-day cycles (ATRA-CHT group, n = 65).
The primary endpoint of the trial was 2-year event-free survival.
Key Findings
Enrollment began in June 2016 and was discontinued prematurely in August 2022 due to slow accrual during the COVID-19 pandemic.
After a median follow-up of 37 months (range = 1.7–88.6 months), 2-year event-free survival was 88% in the ATRA-ATO group vs 71% in the ATRA-CHT group (hazard ratio [HR] = 0.4, 95% confidence interval [CI] = 0.17–0.92, P = .02).
At a median of 7.8 and 12.1 months from achievement of complete remission, molecular relapse occurred in one patient (1.5%) in the ATRA-ATO group vs eight patients (12.3%) in the ATRA-CHT group (P = .014).
The 2-year overall survival rate was 93% in the ATRA-ATO group vs 87% in the ATRA-CHT group (HR = 0.6, 95% CI = 0.2–1.8, P = .36) and the 2-year cumulative incidence of relapse was 1.8% vs 17% (P = .008).
Serious adverse events suspected to be related to treatment occurred in 7 patients (10%) in the ATRA-ATO group and 24 patients (37%) in the ATRA-CHT group (P < .01). Those in the ATRA-ATO group included acute kidney injury, acute pulmonary edema, capillary leak syndrome, differentiation syndrome, and myocarditis (1 patient each); the most common in the ATRA-CHT group were febrile neutropenia (n = 9) and differentiation syndrome (n = 5).
The investigators concluded: “The results of the APOLLO trial support the use of ATO and ATRA for the treatment of newly diagnosed patients with high-risk [acute promyelocytic leukemia].”
Uwe Platzbecker, MD, of University Hospital Carl Gustav Carus and TU Dresden, Dresden, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the German Federal Ministry of Education and Research. For full disclosures of all study authors, visit ascopubs.org.
