For patients with low or intermediate risk acute promyelocytic leukaemia (APL), the standard of care treatment is all-trans retinoic acid (ATRA)-arsenic trioxide (ATO), based on a study reporting benefit of ATRA/ATO over ATRA-chemotherapy.1 However, for patients with high-risk (HR) APL, ATRA + chemotherapy is still the gold standard and ATRA/ATO has not been studied in randomised trials in this patient population. Therefore, the open label, prospective, multicentre phase III APOLLO trial investigated the safety and efficacy of ATRA/ATO in patients with HR-APL.2
This study enrolled 133 patients (median age 46) with newly-diagnosed APL up to the age of 65 years with a white blood cell count at diagnosis of >10 GPt/l, ECOG 0-3, serum total bilirubin and serum creatinine ≤ 3 mg/dl. Patients were randomly assigned to receive either: Arm A; induction therapy with ATRA/ATO until complete response (CR) was achieved, along with two doses of intravenous idarubicin at 12 mg/m². This was followed by 4 cycles of consolidation therapy with ATO on a 4-weeks-on/4-weeks-off schedule and ATRA on a 14-days-on/14-days-off schedule; Arm B; induction therapy with idarubicin and ATRA until CR, followed by consolidation therapy consisting of 15 days of anthracycline-based chemotherapy with idarubicin in the first cycle, 15 days of mitoxantrone in the second cycle, and another 15 days of anthracycline-based chemotherapy with idarubicin in the third cycle. This regimen was then followed by maintenance therapy with 6-mercaptopurine and methotrexate, along with ATRA, for two years.
At a median follow up of 31 months, the incidence of grade 1-4 thrombocytopenia and neutropenia was lower in the ATRA/ATO arm (at induction; thrombocytopenia: 15% vs. 22% (p= 0.293); neutropenia: 22% vs. 46% (p= 0.005)), and during consolidation therapy these toxicities were 0% and 1%, for the ATRA/ATO arm vs. arm B respectively. Further, 93% of patients achieved CR in the ATRA/ATO arm vs. 90% in the ATRA-chemotherapy arm (p=0.654) and the incidence of relapse at two years was 1.6% vs. 14%, respectively (p= 0.011). Overall survival was numerically higher in the ATRA/ATO arm (93% vs. 82%, p= 0.17). Finally, event-free survival at two years was higher in the ATRA/ATO arm (88% vs. 70%, p= 0.02). These results support the superiority of ATRA/ATO over ATRA-chemotherapy in patients with HR-APL.
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