Overall survival and prognostic factors of adult patients with acute promyelocytic leukemia in the pre- all-trans-retinoic acid + arsenic trioxide (ATRA+ATO) era and the post-ATRA+ATO era in the US

Abstract Background Since late 1980s there were no significant therapeutic advances for Acute Promyelocytic Leukemia (APL)1. The results of the APL0406 trial on the combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) for newly diagnosed low-risk APL2 led to its approval in the US. Our hypothesis is that there have been improvements in Overall Survival (OS) after the introduction of ATRA+ATO and we would like to characterize this outcome in real world patients (pts) in the US. Materials and Methods APL pts ≥18 years of age with the ICD-O-3 code 9866/3 were obtained from the Surveillance, Epidemiology, and End Results (SEER) Database from years 2000 to 2020. A cutoff on 2017 was made based on the approval of ATRA+ATO. Statistical analyses were conducted with SPSS®. Pts characteristics were reported in frequencies. The Wilcoxon (Gehan) test was used to compare OS. Cox Regression was done to identify independent prognostic factors of survival. A p-value ≤0.05 was considered statistically significant. Results A total of 104 adults with APL were included (3.7% of Acute Myeloid Leukemia pts). Median age was 61.5 years (interquartile range: 31.5 years). 53.8% were males. 59.6% were Non-Hispanic White, followed by Hispanics (23.1%) and Non-Hispanic Blacks (10.6%). 78.8% lived in metropolitan areas, and 33.7% had income <60,000 US dollars. The division by cohorts showed 77 APL pts in the pre-ATRA+ATO cohort and 27 pts in the post-ATRA+ATO cohort. The 5-year OS was 31% in the pre-ATRA+ATO era vs 52% in the post-ATRA+ATO era (p=0.032). In the whole APL population multivariate analysis, age <60 years (HR=0.56, 95%CI: 0.31- 0.99, p=0.050) and chemotherapy (HR=0.23, 95%CI: 0.12-0.44, p<0.001) were associated with improved OS, independent of other variables analyzed. Conclusions To the extent of our knowledge, this study stands as the first US real world evidence that elucidate survival outcomes in APL pts after the introduction of ATRA+ATO at a population level. The OS effect of this treatment is significant enough to be seen in population-based studies that included pts that could not participate in clinical trials. Limitations include that SEER database does not contain risk stratification, progression-free survival and biomarkers. References 1. Ferrara F et al. Expert Opin Pharmacother. 2022;23(1):117-27. 2. Platzbecker U et al. J Clin Oncol. 2017;35(6):605-12.