Based on the APOL0406 study, ATRA (all-trans retinoic acid) plus ATO (arsenic trioxide) has been a frontline treatment for low- or intermediate-risk acute promyelocytic leukemia (APL). In high-risk APL settings, the ATRA/ATO combination hadn't been studied through randomized trials. At present, the gold standard for high-risk APL (HR-APL) has been ATRA combined with anthracycline-based chemotherapy (the AIDA regimen). Roughly 20% of patients still have relapses in the frontline setting for APL, despite the significant advancements made with ATRA plus anthracycline-based regimens. The positive outcome from the APOLLO study (NCT02688140) is expected to significantly influence and improve future treatment strategies for patients facing high-risk APL.

The international, multicenter, open-label APOLLO trial randomized patients to receive induction therapy with ATO and ATRA until complete response (CR). Although the study ended early due to COVID-19 and drug expiration, it evaluated 131 patients with high-risk APL. Results showed a 2-year event-free survival (EFS) rate of 89% for the ATRA-ATO group, significantly higher than the 72% in the ATRA-chemotherapy group. Overall survival rates were 93% for ATRA-ATO compared to 87% for traditional therapy. With ATRA/ATO and ATRA/chemotherapy, the five-year EFS rates were 87% (95% CI, 79%–96%) and 55% (95% CI, 38%–78%), respectively (p = 0.0034).

The ATRA-ATO regimen also had a superior safety profile, with no molecular relapses versus six in the standard group. These findings suggest that the ATRA-ATO combination offers greater efficacy and safety, likely influencing future high-risk APL treatment strategies.

KOL insights

“We believe that these first results of a first-line therapy with ATRA/ATO with 2 initial doses of idarubicin results in superior EFS compared with conventional ATRA/chemotherapy in patients with high-risk APL. Further analysis of the APOLLO trial may support the implementation of this regimen as the new standard of care in patients with high-risk APL.” – MD, Germany.

Conclusion

About 10% of adult patients with acute myeloid leukemia (AML) have APL. APL has an extremely favorable prognosis in comparison to other leukemias. These days, APL is thought to be the most curable type of adult leukemia because of the advances made in its diagnosis and treatment. About 90% cure rates have been reported from APL treatment institutes.

The APOLLO study tested ATRA/ATO in high-risk settings (WBC count greater than 10,000/μL)  and, despite early termination due to COVID-19 and drug expiration, evaluated 131 patients. Results showed a 2-year EFS of 89% for ATRA-ATO  with OS rates of 93%. These findings highlight that the ATRA-ATO combination not only offers greater efficacy but also enhanced safety, suggesting a promising new standard for high-risk APL treatment.