Improved Real-World Outcomes of Patients with Acute Promyelocytic Leukemia Treated with First-Line Arsenic Trioxide in Specialized Centers in Portugal through a 24/7 Phone-Based Referral: A Study from the Portuguese Acute Leukemia Group

• Published in: Blood 2024-11, Vol.144, p.2894-2894
• Main Authors: Brioso Infante, Joana, Aguiar, Eliana, Sá, Ines, Marques, Ines, Neto, Miguel, Almeida, Catia, Nascimento, Telma, Pereira, Marta Isabel, Cortesao, Emilia, Mendes Sapinho, Guilherme, Medeiros, Julia, Esteves, Graca, Monteiro-Bras, Tiago, Regadas, Luisa, Vieira, Ines, Saraiva, Filipa, Alikhanov, Georgy, Santos, Joana, Ribeiro, Patricia, Trigo, Fernanda
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-210470

Introduction Acute Promyelocytic Leukemia (APL) has evolved from the most lethal into the most curable acute leukemia today, due to targeted treatments such as all-transretinoic acid (ATRA) plus arsenic trioxide (ATO). First-line ATO was adopted in 2017 in Portugal, where APL is exclusively treated in University Hospitals after a 24/7 phone-based referral from community centers made doctor-to-doctor. It is unknown whether the outcomes of patients receiving ATRA + ATO in Portugal mirror the excellent clinical trial results, and if early death (ED) rates have been improved from the pre-ATO era in the country. Methods We conducted an observational, retrospective and multicenter study, including 5 University Hospitals in Portugal. All patients with genetically confirmed APL who received first-line ATO plus ATRA between January 2017 and May 2024 were included, regardless of disease risk. Induction response assessment and molecular measurable residual disease (MRD) monitoring using real-time quantitative PCR were performed as per ELN guidelines. Results A total of 135 patients were included in the study, with a median age of 50 years (range 18-82); 16.3% of patients were over 70 years of age, but only 4.4% had an ECOG performance status ≥2. This cohort was composed mostly of non-high risk APL (92.6%), while 10 patients with high-risk APL received ATO due to contraindications for anthracyclines or age >70 years. Seventy-nine patients (58.5%) first presented to a community hospital and were transferred to the closest APL-treating hospital following a phone contact. The median time between APL suspicion and treatment initiation was 1 day (range 0-14). The 30-day early death (ED) rate was 3.7%, attributable to intracranial bleeding (n=3) and septic shock (n=2). Age was the only statistically significant predictor of ED (OR 1.1 [95%CI 1.0-1.2], p=0.028), with age >75 years increasing the odds of ED 8.9 times (p=0.025). The most frequent complications during ATRA + ATO treatment were febrile neutropenia (75%), bleeding (18.5%), differentiation syndrome (DS) (17.7%) and hepatotoxicity (14.1%). The incidence rate of DS was significantly lower in the 118 patients who received corticosteroid prophylaxis (14.4%) than in the 17 patients who did not (41.1%). Among the 125 patients evaluable for marrow response, 100% achieved hematologic complete response (CR). All the 101 patients who completed the 4 consolidation courses achieved negative molecular MRD. Regarding the role o