Current management and emerging pharmacotherapeutic strategies in acute promyelocytic leukemia.

Abstract

Acute promyelocytic leukemia (APL) has evolved from one of the most rapidly fatal neoplasms into the most curable acute myeloid leukemia subtype, following the sequential clinical introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Despite cure rates now approaching 100% in non-high-risk disease, early death occurring before or shortly after treatment initiation and relapse/refractory APL cases remain the principal obstacles to achieving a definitive cure. This review summarizes current standard-of-care APL management, including risk stratification, induction, consolidation and maintenance strategies. It then reviews emerging pharmacotherapeutic strategies, including oral arsenic formulations, tamibarotene, anti-CD33 antibody-based and cellular therapies, and other investigational agents. A literature search of PubMed/MEDLINE was performed from the 1950s to 2026 using terms including 'acute promyelocytic leukemia,' 'ATRA,' 'arsenic trioxide,' 'oral arsenic,' 'tamibarotene,' 'gemtuzumab ozogamicin,'and other keywords, prioritizing recent randomized trials, prospective studies and expert consensus guidelines. Reducing early mortality through faster diagnostic suspicion, extending chemotherapy-free regimens to high-risk disease, and transitioning toward oral, outpatient-based arsenic formulations represent the most promising paths toward a cure. Tailored strategies for rare variant and resistant APL subtypes, including targeted triplet combinations represent a promising treatment for complex APL case, but warrant structured evaluation in prospective clinical trials.