DP020 | CLINICAL-BIOLOGICAL CHARACTERISTICS AND TREATMENT MODULATION IN AML PATIENTS RECEIVING LONG-TERM (>24 COURSES) TREATMENT WITH HYPOMETHYLATING AGENTS AND VENETOCLAX.

INTRODUCTION. Venetoclax (VEN) in combination with hypomethylating agents (VEN+HMAs) has become the treatment of choice for patients (pts) with AML who are ineligible for IC . The primary goal of this combination is to prolong survival (OS) maintaining a good quality of life. To date, no specific analyses are available on pts receiving long-term treatment with VEN+HMAs. STUDY CHARACTERISTICS. This is an ongoing Italian multicenter study enrolling patients who have received 24 or more cycles of VEN+HMAs. The final sample size will be 100 cases. The study objectives are: to evaluate the characteristics of long-treated pts, to collect information on treatment management (e.g. VEN exposure-days, VEN dose modulations, inter-cycle intervals), to evaluate the timing of complete remission (CR) and MRD. RESULTS. To date, 79 pts with a median age of 77 years and a median of BM blasts at diagnosis of 55% have been included from 25 Italian centers; 15% of cases were FLT3-m and 27% were NPM1-m; 60% had a normal karyotype (only 13%-adverse karyotype). HMA was azacitidine in 67% of cases and decitabine in 33% of cases. The median number of cycles was 32 (range, 24-55) with 57% of pts receiving more than 30 cycles. NGS data are available in 33% of pts (with DNMT3-m 38% and IDH2 or IDH1-m 39%). CR occurred in the majority of pts (90%) by cycle 2. MRD was assessed in 90% of pts (by flow cytometry and/or molecular markers) and 49% of assessed cases achieved an early MRD negativity. The median number of days of VEN exposure was 21 in the first 3 cycles, 14 up to cycle 26, and then decreased to 7-10 days in the subsequent cycles. The VEN dose was adjusted in most cases. The median interval between cycles was 35 days until cycle 26 and then increased to 45 days. At the last follow-up, the discontinuation rate was 27% (21/79) and the main reason for discontinuation was relapse (71%-15/21). In 3 pts, treatment was stopped (after 24, 26, and 29 cycles) based on the decision of the treating physician due to persistence of MRD negativity. The probability of OS at 60 months was 56%. CONCLUSIONS. The data obtained from long-term VEN+HMAs treated pts (24 cycles or more in this study) may be useful for improving clinical practice. In particular, they may help to optimize VEN exposure and inter-cycle interval in the long-treated cases, to identify the baseline profile of pts who are more likely to have a long lasting and deeper response and to properly select CR pts who may be the best candidates for treatment discontinuation.