The treatment of acute promyelocytic leukemia in 2023: Paradigm, advances, and future directions

Abstract

The transformation of acute promyelocytic leukemia (APL) from an often fatal to highly curable cancer with long-term survival exceeding 90% is one of the greatest and most inspiring successes in oncology. A deeper understanding of the pathogenesis of APL heralded the introduction of highly effective therapies targeting the mutant protein that drives the disease, leading to the chemotherapy-free approach to cure almost all patients. In this review, we discuss the paradigm of treatment of APL in 2023, reinforce the high risk of early death without prompt initiation of treatment at first clinical suspicion, and dedicate a special focus to novel agents and future directions to improve cure rates and quality of life in patients affected by APL.

Superiority of anthracycline‐free treatment in standard‐risk acute promyelocytic leukemia: A systematic review and comparative epidemiological analysis

“…informed consent gained [8], outcome measures reliable [9], outcome measures valid [10], intervention described in detail [11], contamination avoided [12], cointervention avoided [13], statistical reporting of results [14], appropriate statistical analysis [15], clinical importance reported [16], drop-outs reported [17], appropriate conclusions [18], clinical implications reported [19], study limitations acknowledged [20]. Studies were rated as poor (<7 points), moderate (7-11 points), good (12-15 points), very good (16-18 points), or excellent quality (19-20 points).…”

“…However, insightful research has uncovered the efficacy of all‐trans retinoic acid (ATRA) 5 and arsenic trioxide (ATO) 6 in APML treatment—leading to a much‐improved prognosis with 6‐year disease free survival rates as high as 96% 7 . Studies demonstrating non‐inferiority of chemotherapy‐free alternatives in induction 8,9 and consolidation 10 have informed a recent shift in clinical practice toward the omission of anthracycline in treatment regimens 11 . However, these treatment decisions are complicated by the severity of the disease itself at presentation with much of the treatment based on risk stratification.…”

Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia in the ATRA/ATO Era

“…Despite the advances in APL therapy through the introduction of differentiationinducing agents, there is still a proportion of 5-20% of cases that relapse [9,10,13]. In the great majority of cases, relapse occurs during the first three years [2,32].…”

“…Although consolidation with HSCT shows improved outcomes, it appears that a significant subset of patients could experience long-term survival with ATO-based postremission therapy [9]. An interesting data set comes from studies that enrolled patients with relapsed APL who obtained a second molecular CR, who were offered auto-HSCT but could not continue with this procedure for non-medical reasons, usually because of financial constraints or patient choice, and who received ATO-based consolidation.…”

“…The limitations of the clinical use of HSCT in APL are related to factors specific to the patient (age, comorbidities, donor availability), disease-specific variables (MRD status before HSCT, CR1 duration), therapy-specific factors (toxicity, impact on QoL) and other non-medical issues (financial/administrative constraints, patients' choice) [9,41,78]. Highdose conditioning chemotherapy for auto-HSCT is associated, in rare cases, with the risk of secondary malignancies (myelodysplastic syndrome, AML) [9,10,42,47]. This raises the question of whether some patients in CR2 may be consolidated without transplantation, especially those with a family history suggestive of myeloid neoplasms (which should be tested for germline predisposition mutations) [9,10].…”