Drug treatment options for acute promyelocytic leukemia

ABSTRACT

Introduction

Until the late 1980s, acute promyelocytic leukemia (APL) was the most rapidly fatal leukemia; however, nowadays, it is a curable disease with survival rates exceeding 90–95%. The improvement of APL outcome is mainly due to two agents, which target the typical translocation t(15;17) and its fusion transcript PML-RARα responsible for initiating and maintaining the disease: all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). The story of APL represents a pioneering model for the development of precision medicine and curative chemotherapy-free approaches for acute leukemia.

Area covered

The authors examine the major advances in the treatment of patients with APL focusing on three different eras: 1) the pre-ATRA era; 2) the ATRA era; 3) the ATO era.

Expert opinion

The combination of ATRA and ATO is effective and curative for the majority of APL patients. It has been approved for low/intermediate risk cases while an experimental trial with a minimal addition of chemotherapy for high-risk ones is ongoing. Disease relapse is infrequent and can be cured with ATRA-ATO rechallenging, with or without subsequent transplantation depending on the interval between complete remission and relapse. New therapeutic landscapes contemplate the use of an oral chemo-free ATRA-ATO combination, implementing treatment as outpatient care, thus increasing quality of life and decreasing medical costs.

KEYWORDS:

• Acute promyelocytic leukemia
• risk-adapted strategies
• chemo-free approach
• arsenic trioxide
• oral arsenic derivatives

Article Highlights

• Progressive advances in the therapeutic approach of acute promyelocytic leukemia have changed the prognosis of the disease to evolve from a potentially fatal disease to the most curable subtype of acute myeloid leukemia.

• All newly diagnosed non-high risk patients should receive induction and consolidation treatment with the combination of ATRA and ATO.

• Currently available data from studies in HR patients with ATO-ATRA combined with chemotherapy do still not allow for recommendation of a specific regimen. Accordingly, these patients should receive conventional treatment with ATRA plus chemotherapy or be enrolled in prospective clinical trials.

• The early mortality rate in the real life remains high, ranging between 18 and 30%, due to early death occurring before having a molecular diagnosis; explanations include a clinical presentation that can be misunderstood in emergency units or peripheral institutions.

• The differentiation syndrome (DS) is a potentially life-threatening complication in the ATRA and/or ATO treatment, with a frequency being around 25%, usually occuring within one to two weeks after initiation of treatment. The administration of steroids (prednisone) during induction with ATRA and/or ATO is currently suggested to decrease the risk of DS

• Evaluating future perspectives, for a new era in the APL treatment, it is likely that oral arsenic derivatives will substitute the intravenous formulation, resulting in combination with ATRA an entirely oral management of the disease, increasing quality of life and lower medical costs.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.