Arsenic Trioxide Plus ATRA: A Better Option for Patients With Acute Promyelocytic Leukemia?

The combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) could be a safer and more effective treatment option than ATRA and chemotherapy for patients with acute promyelocytic leukemia (APL), leading to higher event-free survival (EFS), according to research correspondence from Francesco Lo-Coco, MD, from the University Tor Vergata in Rome, Italy, and colleagues that was published in The New England Journal of Medicine.1

“Treatment outcomes in patients with newly diagnosed APL have improved dramatically in the two decades since the advent of ATRA and ATO,” Dr. Lo-Coco and colleagues wrote. “However, long-term results for this strategy are still awaited.”

“ATRA combined with chemotherapy results in cure rates above 80 percent; however, it is associated with a risk of severe infections and secondary leukemias,” the authors explained. “ATO combined with ATRA has proved at least equally effective and has more manageable toxic effects.”

In the randomized APL0406 trial, researchers compared the two approaches (ATRA + chemotherapy vs. ATRA + ATO) in patients with non–high-risk APL, defined as having white-cell counts ≤10 × 109/L. Earlier results from the trial showed that, after a median follow-up of 34 months, patients in the ATRA + ATO group achieved a significantly higher rate of EFS at two years than those in the ATRA + chemotherapy group (97% vs. 86%; p=0.02).2

In this update, 156 patients were included in an intent-to-treat analysis and followed for a median of 53 months.

At 50 months, the EFS rate was again higher in the ATRA + ATO group than in the ATRA + chemotherapy group: 96 percent (95% CI 92-100) versus 81 percent (95% CI 73-91; p=0.003). The overall survival rate was also higher: 99 percent (95% CI 96-100) versus 88 percent (95% CI 81-96; p=0.006).

Post-remission events in the ATRA + chemotherapy group included six relapses and five deaths (one of which was due to secondary leukemia). In the ATRA + ATO group, there were two relapses and one death in remission; no further events had been recorded in this treatment group since the earlier publication of results.

Because the APL0406 trial enrolled patients with non–high-risk APL, these results are not applicable to patients with high-risk APL. “Given the low number of patients with high-risk disease who were enrolled in [a similar, multicenter, randomized trial] from the UK National Cancer Research Institute, we believe that a randomized trial comparing ATRA + arsenic trioxide with ATRA + chemotherapy in such patients is still needed,” the authors concluded.

Inclusion criteria and the small number of patients enrolled may affect the generalizability of study results. The study, which was conducted at centers in Austria, Germany, and Italy, also did not address the insurance obstacles to receiving outpatient therapy that APL patients may face in other countries.


References

  1. Lo-Coco F, Di Donato L, Schlenk RF. Targeted therapy alone for acute promyelocytic leukemia. N Engl J Med. 2016;374:1197-8.
  2. Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369:111-21.

SHARE