P202 | FRONTLINE NILOTINIB VS DASATINIB IN NEWLY DIAGNOSED CHRONIC PHASE CHRONIC MYELOID LEUKEMIA: A PROPENSITY SCORE ANALYSIS BASED ON AIFA MONITORING REGISTRIES

Frontline second generation tyrosine kinase inhibitors increased the rate of deep molecular responses (DMR) but were also mined by increased related adverse events. A single Asiatic trial randomized the two drugs, dasatinib and nilotinib without differences in efficacy. Aim: the aim of this analysis is to evaluate the time to discontinuation among the two drug-defined groups after balancing for the available baseline characteristics. A nationwide real-world retrospective cohort study including all newly diagnosed chronic phase CML adult Italian patients who started dasatinib or nilotinib from January 2013 to December 2016. Dasatinib and nilotinib posology and administration were in accordance to EU SmPC recommendations. The decision to prescribe either of the two drugs was based on treating physician clinical judgement. The main outcome considered is time to treatment discontinuation (TTD). TTD was compared among the two groups after balancing for the available baseline characteristics. Median TTD and follow-up were obtained using the Kaplan-Meier and Reverse Kaplan-Meier respectively. Baseline characteristics of the two groups was balanced using weights obtained from a gradient boosting machine algorithm (gbm). The methodology is based on an average treatment effect for the treated (ATE) Inverse Probability Treatment Weighting (IPTW) (REF) approach to estimate propensity scores from the gbm model and obtain the relative weights. Overall, 1526 patients were analyzed (628 treated with dasatinib and 898 with nilotinib), with a male prevalence (56.2%) and a median age of 54.1 years (57.3 in dasatinib cohort and 51.9 in nilotinib group). Sokal score identify a low risk in 40.8%, intermediate 37.8% and a high risk in 21.4% (26.4% with dasatinib and 17.8% with nilotinib, respectively). After a median follow-up of 4.9 years and post-adjustment, the median time in treatment was 53.5 months with dasatinib and 70.5 with nilotinib (HR 0.61, 95% CI 0.54-0.69, p<0.0001). The TTD at 24 and 48 months with nilotinib was 0.79 (0.77-0.82) and 0.68 (0.65-0.72), respectively and with dasatinib was 0.73 (0.70-0.77) and 0.55 (0.51-0.60), respectively. A comparison between the two drugs for selected covariate categories, showed, among all selected variables, a lower risk of treatment discontinuation associated to the nilotinib treatment. With the limitation of a real-world analysis based on AIFA registries, and the lack of data about the reasons for discontinuation, we showed a longer probability of treatment with frontline nilotinib. This data suggests the need for further investigations on treatment discontinuation causes especially to evaluate any involvement on the observed differences due to differences between the two drugs tolerability profiles.