Chemotherapy-free approaches to newly-diagnosed acute promyelocytic leukemia: is oral-arsenic trioxide/all-trans retinoic acid/ascorbic acid the answer?

ABSTRACT

Introduction

Acute promyelocytic leukemia (APL) is a distinct form of acute myeloid leukemia characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion. Frontline use of intravenous arsenic trioxide (i.v.-ATO) and all-trans retinoic acid (ATRA) has vastly improved cure rates in APL. Researchers in Hong Kong invented the oral formulation of ATO (oral-ATO) and have confirmed a bioavailability comparable to i.v.-ATO. A plethora of studies have confirmed the safety and efficacy of oral-ATO-based regimens in the frontline and relapsed setting.

Areas covered

Aspects on the development of oral-ATO-based regimens for APL in the frontline and relapsed setting are discussed. The short-term and long-term safety and efficacy of oral-ATO-based regimens are discussed. The frontline use of oral-ATO in combination with ATRA and ascorbic acid (AAA) induction in a ‘chemotherapy-free’ is highlighted.

Expert opinion

Current and ongoing data on the use of oral-ATO-based regimens in APL support the use of oral-ATO as an alternative to i.v.-ATO allowing a more convenient and economical approach to the management of APL.

KEYWORDS:

• Oral arsenic trioxide
• all-trans retinoic acid
• ascorbic acid
• chemotherapy-free
• acute promyelocytic leukemia

Disclaimer

As a service to authors and researchers we are providing this version of an accepted manuscript (AM). Copyediting, typesetting, and review of the resulting proofs will be undertaken on this manuscript before final publication of the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal relate to these versions also.

Declaration of interest

H Gill is employed by the University of Hong Kong which currently holds two United States (US) patents (7,521,071 B2 and 8,906,422 B2), one Japanese patent (4786341) and one European patent (EP 1562616 B1) for the use of oral-ATO in the treatment of leukemias and lymphomas. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Acute promyelocytic leukemia (APL) is characterized by the presence of t(15;17)(q24;21) and the PML:RARA gene fusion.

• Researchers in Hong Kong invented the oral formulation of arsenic trioxide (oral-ATO) and have confirmed a bioavailability comparable to intravenous arsenic trioxide (i.v.-ATO).

• Efficacy and safety of oral-ATO-based regimens have been confirmed in the clinical trial setting and long-term follow-up studies.

• ATO acts synergistically with ascorbic acid and thus ascorbic acid is incorporated into oral-ATO based regimens.

• The combination of oral-ATO, all-trans retinoic acid (ATRA) and ascorbic acid (AAA) in the frontline induction setting is high efficacious and safe with survivals comparable to that seen with i.v.-ATO based regimens.

• With a frontline oral-AAA-based induction in a risk-adapted manner, the use of chemotherapy is minimized.

• Oral-ATO represents an alternative to i.v.-ATO and can be incorporated into the current frontline induction regimens for APL.

Additional information

Funding

This paper was funded by the Health and Medical Research Fund, Health Bureau (project number: 08191946) and the Innovation and Technology Fund, Innovation and Technology Commission (project code: PRP/029/22FX) of the Government of the Hong Kong Special Administrative Region.