Minimal Residual Disease Evaluation in Acute Myeloid Leukemia patients treated with Venetoclax and Hypomethylating Agents

Acute myeloid leukemia (AML) is a genetically heterogeneous malignant clonal disorder of the hematopoietic system. Treatment of older patients with AML is quite challenging, an older age is independently associated with an inferior outcome. Hypomethylating agents such as 5-azacytidine and decitabine, has shown to be a promising option for older patients with AML, who are not suitable candidates for intensive therapies. Venetoclax (VEN) is an oral, potent, and selective BCL2 inhibitor. Synergistic activity against myeloid malignancies is seen in vitro and in vivo with VEN in combination with lower intensity antileukemia therapy, such as low-dose cytarabine (LDAC) or hypomethylating agents (HMA). This project, aims to analyze the response of AML patients to Venetoclax and monitored by MRD assay (multiparameter flow cytometry or MFC) We will collect data on consecutive patients affected by de novo or secondary AML according to WHO 2016 criteria, in relapse or refractory phase of disease. Data will include clinical data and response data (minimal residual disease tested by multiparameter flow cytometry or MFC). The combined therapy of Venetoclax and HMA resulted in good responses, especially in chemo-refractory patients and allogeneic transplant candidates. The quality of the responses made it possible, in a good percentage, to achieve allogeneic transplantation in MRD-negativity conditions. The recurrence of treatment-associated neutropenia was the most frequent reason for temporary treatment discontinuation, consequently a document for the management of neutropenia was drawn up, derived from the various indications in the literature. Despite the good results achieved, resistance to venetoclax and the possibility of discontinuing treatment once deep and lasting complete remission has been achieved remain open questions.