All-Oral Regimen Feasible and Effective in Acute Promyelocytic Leukemia, Study Finds

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An all-oral regimen for newly diagnosed acute promyelocytic leukemia (APL) was shown to be “highly effective and safe,” eliminating the need for chemotherapy altogether in many patients, Hong Kong researchers reported at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition.1 Additional studies are being planned to further assess the use of intravenous and oral formulations of arsenic trioxide as front-line treatment of APL.

In the study, patients with APL who received a synergistic combination of arsenic trioxide, all-trans retinoic acid, and ascorbic acid (AAA) in oral form, with little to no chemotherapy, achieved high overall survival and relapse-free survival rates at 3 years, according to Harinder Gill, MD, MBBS, FRCP, FRCPath, Clinical Associate Professor at the University of Hong Kong.

Harinder Gill, MD, MBBS, FRCP, FRCPath

Harinder Gill, MD, MBBS, FRCP, FRCPath

“This entirely oral regimen is highly effective, safe, and can be administered in an outpatient setting for all risk categories,” he said. “In addition, we found we can minimize chemotherapy in patients with all risk levels—not only in lower-risk patients—as well as in both pediatric and adult patients.”

This is the first survival data for an entirely oral AAA regimen in patients with both high- and standard-risk types of APL, a rare hematologic malignancy in which abnormal promyelocytes harboring the PML::RARA fusion oncogene accumulate in the bone marrow. Historically, the standard of care for both newly diagnosed and relapsed APL has included intravenous administration of arsenic trioxide and chemotherapy. This regimen can induce remissions in more than 90% of patients, but the intravenous approach requires repeated hospital admissions and causes treatment-related toxicities.

“Early death is still a major problem, and real-world outcomes are much worse than those in clinical trial and academic settings. Access to intravenous all-trans retinoic acid is also limited in resource--constrained countries, and there is a need to reduce chemotherapy, to mitigate short-term and long-term toxicities,” Dr. Gill said.

The study evaluated molecular responses during treatment with oral AAA-based induction, consolidation, and maintenance. The all-oral regimen was designed for all risk and age groups, with the arsenic trioxide dosage adjusted by weight. The Hong Kong investigators hold the patent for this product, which they also export around the world, Dr. Gill explained.

Study Details

The study enrolled 125 patients (median age = 49), including 5 patients younger than age 18, with newly diagnosed APL drawn from sites in Hong Kong, Singapore, and mainland China between 2018 and 2023. A total of 93 patients (74%) had standard-risk disease (presentation leukocytes ≤ 10 × 109/L), and 32 (26%) had high-risk disease (leukocytes > 10 × 109/L). Of these patients, 8 died before induction and 117 received oral AAA-based induction on protocol; for 79%, this was AAA alone, whereas for 21%, who were younger, high-risk patients, a 3-day course of intravenous daunorubicin was also given. Overall survival, relapse-free survival, and safety were the study’s primary endpoints.

Key Findings

All 117 patients achieved a complete response to the all-oral AAA regimen. At data cutoff, 63 patients had completed 2 years of maintenance therapy. After a median follow-up of 31 months, the rates of 3-year overall survival and relapse-free survival were both 97%. Two deaths occurred during follow-up: one patient relapsed and died of refractory APL, and another died of unrelated gastrointestinal bleeding while in remission, Dr. Gill said.


  • An all-oral regimen of arsenic trioxide, all-trans retinoic acid, and ascorbic acid for newly diagnosed patients with acute promyelocytic leukemia was shown to be highly effective and safe.
  • All 117 patients, some at standard risk and some at high risk, achieved a complete response, and the regimen was reported to be well tolerated.
  • At 3 years, both recurrence-free and overall survival rates were 97%.

Although intravenous and oral doses of arsenic trioxide have similar bioavailability, peak levels can be higher shortly after intravenous dosing, and this can put patients at risk for QTc prolongation, Dr. Gill shared. With the all-oral regimen, no cardiotoxicity was observed, and the most common nonhematologic toxicities were low-grade headache (36%) and transaminitis (50%). APL differentiation syndrome, a known complication of treatment with all-trans retinoic acid and arsenic trioxide, occurred in 58% of patients after initiation of AAA, all within the first 2 weeks and all responding fully to standard intravenous steroids. There were no toxicity-related discontinuations or treatment-related deaths. 

DISCLOSURE: Dr. Gill reported financial relationships with Bristol Myers Squibb, Pfizer, Imago BioSciences, GSK, Novartis, and PharmaEssentia.


1. Gill H, Yim R, Chin L, et al: An entirely oral regimen of oral-arsenic trioxide/all-trans retinoic acid/ascorbic acid in newly diagnosed acute promyelocytic leukemia: Updated results of an ongoing multicenter trial. 2023 ASH Annual Meeting & Exposition. Abstract 157. Presented December 9, 2023.

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