Combination of Venetoclax and Hypomethylating Agents in Relapsed/Refractory Acute Myeloid Leukemia: Single-Center Clinical Experience

Context We report patients with R/R-AML who were treated with venetoclax and hypomethylating agent (HMA). Objective Venetoclax is an oral selective inhibitor of antiapoptotic protein BCL-2, which is overexpressed in AML and associated with poor prognosis. Venetoclax is used in combination with HMA for newly diagnosed AML patients who are elderly or unfit for standard intensive induction/salvage therapies. Design We analyzed 4 R/R-AML patients who were treated with venetoclax and HMA, retrospectively. Patients Case 1: A 45-year-old male patient developed multiorgan failure (MOF) after 3+7 induction chemotherapy. He was followed up in intensive care unit (ICU) for 17 days. He achieved complete remission (CR) after induction. He received two cycles of 5-azacytidine for maintenance. He relapsed and had decitabine and venetoclax. He achieved CR after two cycles. He relapsed in follow-up and passed away from sepsis. Case 2: A 45-year-old male patient diagnosed with MDS transformed AML. After 3+7 induction chemotherapy, he had recurrent pneumonia and a breast abscess. After two cycles of azacytidine, he had still refractory disease. He was shifted to decitabine and venetoclax. He required ICU for gastrointestinal bleeding and passed away. Case 3: A 63-year-old female had a serious anal abscess after 3+7 induction chemotherapy. She had persistent MRD after 4 cycles of decitabine, she received 4 cycles of azacytidine and venetoclax. She remains in CR for 10 months of venetoclax/azacytidine. Case 4: 66-year-old male, after 3+7 induction and 4 consolidation cycles of HDAC, he was in CR. Two years later, he relapsed and achieved CR with FLAG; then, he underwent allo-SCT. Six years later, his disease relapsed and he had 6 cycles of azacytidine again. He had CR but relapsed 1 year later. Two cycles of venetoclax and azacytidine were administered. He had recurrent pneumonia and passed away from hemorrhagic cardiac tamponade. Results Three patients showed no response and developed fatal infections with MOF. Only one patient had CR and she has been treated with venetoclax/5-azacytidine for 10 months. Conclusion These outcomes indicate the feasibility of using venetoclax combination with hypomethylating agents. This approach is a salvage option for preventing the use of standard chemotherapy. We report patients with R/R-AML who were treated with venetoclax and hypomethylating agent (HMA). Venetoclax is an oral selective inhibitor of antiapoptotic protein BCL-2, which is overexpressed in AML and associated with poor prognosis. Venetoclax is used in combination with HMA for newly diagnosed AML patients who are elderly or unfit for standard intensive induction/salvage therapies. We analyzed 4 R/R-AML patients who were treated with venetoclax and HMA, retrospectively. Case 1: A 45-year-old male patient developed multiorgan failure (MOF) after 3+7 induction chemotherapy. He was followed up in intensive care unit (ICU) for 17 days. He achieved complete remission (CR) after induction. He received two cycles of 5-azacytidine for maintenance. He relapsed and had decitabine and venetoclax. He achieved CR after two cycles. He relapsed in follow-up and passed away from sepsis. Case 2: A 45-year-old male patient diagnosed with MDS transformed AML. After 3+7 induction chemotherapy, he had recurrent pneumonia and a breast abscess. After two cycles of azacytidine, he had still refractory disease. He was shifted to decitabine and venetoclax. He required ICU for gastrointestinal bleeding and passed away. Case 3: A 63-year-old female had a serious anal abscess after 3+7 induction chemotherapy. She had persistent MRD after 4 cycles of decitabine, she received 4 cycles of azacytidine and venetoclax. She remains in CR for 10 months of venetoclax/azacytidine. Case 4: 66-year-old male, after 3+7 induction and 4 consolidation cycles of HDAC, he was in CR. Two years later, he relapsed and achieved CR with FLAG; then, he underwent allo-SCT. Six years later, his disease relapsed and he had 6 cycles of azacytidine again. He had CR but relapsed 1 year later. Two cycles of venetoclax and azacytidine were administered. He had recurrent pneumonia and passed away from hemorrhagic cardiac tamponade. Three patients showed no response and developed fatal infections with MOF. Only one patient had CR and she has been treated with venetoclax/5-azacytidine for 10 months. These outcomes indicate the feasibility of using venetoclax combination with hypomethylating agents. This approach is a salvage option for preventing the use of standard chemotherapy.