C029 | DO APL PATIENTS TREATED WITH ATO+ATRA ACHIEVE A NORMAL LIFE EXPECTANCY? INSIGHTS FROM THE LONG-TERM FOLLOW-UP OF THE GIMEMA APL0406 TRIAL AND THE REAL-LIFE APL0618 STUDY

Background: The treatment of Acute Promyelocytic Leukemia (APL) has undergone a paradigm shift with the introduction of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA), resulting in significantly improved remission and survival rates. The GIMEMA APL0406 trial (Lo-Coco et al., NEJM 2013) demonstrated the superiority of ATO+ATRA over chemotherapy in low- and intermediate-risk APL. Whether long-term survival of APL patients treated with ATO+ATRA aligns with that of the general population has never been systematically investigated. To address this question, we conducted a combined analysis of the GIMEMA APL0406 and APL0618 trials, being the latter a real-world observational study including patients treated with ATO+ATRA in routine clinical practice. Methods: Data from two independent cohorts of low- to intermediate-risk APL patients treated frontline with ATO+ATRA were analyzed. In APL0406, only patients in the experimental arm were included. APL0618 is a prospective-retrospective observational study reflecting outcome of ATRA-ATO in the real-life treatment context. The Standardized Mortality Ratio (SMR) was calculated as the ratio of observed to expected deaths, with 95% confidence intervals (CIs), based on a Poisson distribution. Expected mortality was estimated using age-, sex-, and region-adjusted mortality tables from the Italian National Institute of Statistics (ISTAT). Results: 129 patients (60 males, 69 females ), median age 46 years, derived from the APL0406 cohort and were analysed at a median follow-up 5.6 years. Geographically: 39 were from Northern Italy, 16 from Central Italy, 74 from Southern Italy/abroad. Two deaths were observed vs. 2.24 expected, SMR 0.89 (95% CI: 0.11–3.23). The APL0618 cohort included 120 patients (59 males, 61 females), of a median age of 52 years, 79 from Northern, 22 from Central, and 20 from Southern Italy. Two deaths occurred vs. 1.71 expected, SMR 1.17 (95% CI: 0.14–4.21). In the combined cohort (N=249), 4 deaths were observed vs. 3.95 expected, SMR 1.01 (95% CI: 0.27–2.59). Conclusions: These findings suggest that low to intermediate risk APL patients treated with ATO+ATRA may achieve long-term survival comparable to that of the general population. Importantly, the consistency of the SMR across both the randomized clinical trial and the real-life study confirms the effectiveness and safety of this chemotherapy-free regimen, beyond the experimental setting. The real-life data provide robust evidence that ATO+ATRA treatment yields similarly favorable outcomes when applied in everyday clinical practice.