Acute Promyelocytic Leukemia: Long-Term Outcomes from the HARMONY Project.

Purpose: Treatment outcomes for acute promyelocytic leukemia (APL) have improved with the widespread use of targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Our study aimed to validate these data in a large patient cohort, and to redefine prognostic factors.

Patients and methods: Leveraging the HARMONY Platform, we analyzed 1438 newly-diagnosed APL patients, diagnosed between 1999 to 2022. Patient data derived from the 2 international multicenter GIMEMA-APL0406 and NCRI-AML17 trials, and 4 European registries (HOVON, AMLSG, Swedish AML Registry and SAL).

Results: The study cohort included 721 males and 717 females, with a median age of 50.5 years (range 16-94 years). Of 1309 patients starting therapy, 562 received ATRA-ATO, and 747 AIDA-like chemotherapy. Early death (ED) occurred in 85 of 1438 patients (5.9%) at a median of 9 days after APL diagnosis and was independently associated with increasing age and high Sanz risk score (OR:1.06, 95% C.I: 1.04-1.08, and OR:4.65, 95% C.I.:2.55-8.51, respectively).The median follow-up was 5.5 years (IQR=3.2-7.5). ATRA-ATO regimen was associated with the best outcome, reaching 91% 7-year overall survival (vs 81% for AIDA-like, HR:2.14, 95%C.I.:1.51-3.05), 89% event-free survival (vs 71% for AIDA-like, HR:2.72 95%CI: 2.01-3.69) and 3% relapse (vs 13% for AIDA-like, HR:4.19, 95%CI:2.38-7.39, p<0.001 for all outcomes). The survival advantage of ATRA/ATO was independent of patients' age, Sanz-risk score, and treatment scenario.

Conclusions: Our study confirms the superiority of ATRA-ATO over ATRA-chemotherapy in APL patients. ED represents an unmet medical need, in particular in older patients and in high-risk APL.