Improved Outcomes Reported With Retinoic Acid and Arsenic Trioxide vs Retinoic Acid and Chemotherapy in APL

Key Points

  • Final results of the phase III APL0406 trial show prolonged event-free survival with ATRA-ATO vs ATRA-chemotherapy in patients with low- or intermediate-risk APL.
  • ATRA-ATO was associated with an overall survival benefit.

As reported in the Journal of Clinical Oncology by Platzbecker et al, the final results of the Italian-German phase III APL0406 trial indicate that the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO [Trisenox]) is associated with better outcomes than standard ATRA plus chemotherapy in first-line treatment of low- or intermediate-risk acute promyelocytic leukemia (APL). The previously reported primary analysis of the study indicated noninferiority of ATRA-ATO in 2-year event-free survival.

Improved Outcomes

In this open-label noninferiority trial, 266 patients were randomized between October 2007 and January 2013 to receive ATRA-ATO (n = 129) or ATRA-chemotherapy (n = 137). Among 263 patients evaluable for induction response, complete remission was achieved in 127 of 127 (100%) ATRA-ATO patients and 132 of 136 (97%) ATRA-chemotherapy patients (P = .12). After median follow-up of 40.6 months, 50-month rates were 97.3% vs 80% for event-free survival (P < .001), 1.9% vs 13.9% for cumulative incidence of relapse (P = .0013), and 99.2% vs 92.6% for overall survival (P = .0073).

Postinduction events included relapse in 2 patients and 1 death in complete remission in the ATRA-ATO group and molecular resistance after third consolidation in 2 patients, 15 relapses, and 5 deaths in complete remission in the ATRA-chemotherapy group. Treatment-related neoplasms occurred in 2 ATRA-chemotherapy patients.

The investigators concluded: “These results show that the advantages of ATRA-ATO over ATRA-chemotherapy increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATRA-ATO compared with ATRA-chemotherapy in low- and intermediate-risk APL.”

The study was supported by the Gruppo Italiano Malattie Ematologiche dell’Adulto Foundation, Associazione Italiana Contro le Leucemie, Linfomi e Mieloma, Associazione Italiana per la Ricerca sul Cancro, and the German Federal Ministry of Education and Research.

Francesco Lo-Coco, MD, of the University Tor Vergata, Rome, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.