Outcomes of Relapsed or Refractory Acute Myeloid Leukemia Patients Failing Venetoclax Based Salvage Therapies.

OBJECTIVES AND METHODS We conducted a retrospective analysis to evaluate the outcomes of 28 heavily pre-treated (median 3 (2-6) treatment lines, sixteen (57%) allotransplanted) relapsed/refractory acute myeloid leukemia patients who had failed salvage Venetoclax based therapies. RESULTS The median age was 59 years (20-80), 20 patients (71%) had ECOG 2-4 status and 18 patients (64%) were stratified to European Leukemia Network 2017 adverse risk group. The most common mutations were ASXL1 (21%), RUNX1 (18%), FLT3 ITD/TKD (18%), PTPN11 (15%), NRAS/KRAS (15%) and WT1 (15%). Twenty-two patients (79%) received different post-Venetoclax salvage therapies with the overall response rate of 23% (complete remission + morphological leukemia-free state). Three of six (50%) patients achieved complete remissions after therapy with Venetoclax + Actinomycin D ± low dose Cytarabine. The remaining 6 patients did not receive any further salvage treatment mainly due to poor general condition. The median overall survival was 3.9 months for all patients (4.3 for those receiving post-Venetoclax salvage vs 1.3 months receiving palliative care alone, p<0.001). CONCLUSIONS Though, the remission rate and survival of patients failing Venetoclax are poor, a small proportion of these R/R AML patients may still respond to cautious intensification of chemotherapy with Venetoclax.