Effective Treatment with Venetoclax and Hypomethylating Agents for the Coexistence of Multiple Myeloma and Acute Myeloid Leukemia: A Case Report and Literature Review.

Objective: Multiple myeloma (MM) and Acute myeloid leukemia (AML) are distinct hematologic malignancies originating from different cell lineages. Their coexistence is extremely rare, and current treatment approaches are even more so. Therefore, exploring the clinical features of their coexistence and the promising treatment strategy is worthwhile.

Case report: We described three cases involving the coexistence of MM and DNMT3A-mutant AML, two of which presented simultaneous occurrences, while Case 3 had secondary AML about 70 months after the MM.

Discussion: All cases exhibited DNMT3A mutations, which characterized by one missense mutation and two frameshift mutations; all were likely loss of function mutations. Among them, two patients were treated with Venetoclax-based regimens and achieved favorable effects. The patients were alive for 62,38 and 103 months.

Conclusions: Clonal hematopoiesis of DNMT3A may have a crucial role in the coexistence of MM and AML and Venetoclax-based regimens reveal favorable treatment responses. However, drug resistance still needs to be considered, and further research is required to elucidate the underlying mechanisms and treatment strategies.