Case of Therapy-Related AML and Myeloma: Decitabine/Venetoclax and Daratumumab
Posted: Monday, May 17, 2021
In a recent Letter to the Editor published in Annals of Hematology, researchers from the University of Freiburg, Germany, reported on a case study of a patient diagnosed with high-risk multiple myeloma who developed therapy-related acute myeloid leukemia (AML). Treatment of AML consisted of decitabine/venetoclax, and daratumumab was given to treat progressive multiple myeloma. Monika Engelhardt, MD, PhD, of the University of Freiburg, and colleagues hypothesized that “upregulation of CD38 in bone marrow plasma cells after decitabine/venetoclax may have enhanced [the] multiple myeloma response.”
“Clinical trials are currently under way to investigate whether pretreatment with demethylating agents enhances the efficacy of daratumumab,” the authors noted.
A 64-year-old female diagnosed with stage III IgG kappa multiple myeloma presented with anemia and osteolytic lesions. A 90% infiltration of bone marrow plasma cells (BMPCs) as well as hyperdiploidy and del 17p13. The combination of bortezomib, cyclophosphamide, and dexamethasone was first-line treatment followed by autologous stem cell transplantation. Therapy related AML was confirmed using flow cytometry analysis upon worsening pancytopenia and BMPCS of 50% and myeloid blasts of 22%. Molecular analysis revealed mutations in DNMT3A and IDH1.
The patient experienced complete remission of AML after treatment with decitabine/venetoclax. Second-line daratumumab was started upon multiple myeloma progression. A 90% upregulation of CD38 plasma cells was seen in plasma cells using immunohistochemistry. Daratumumab treatment resulted in a very good partial response and improved peripheral blood counts (hemoglobin, leukocytes, and platelets). However, the patient died due to the progression of both AML and myeloma, 50 months after the diagnosis of myeloma and 9 months after the diagnosis of therapy-related AML.
Based on the authors' case study and literature review, treatment options to enhance CD38 expression may prove to be viable options in adults with multiple myeloma and AML.
Disclosure: For full disclosures of the study authors, visit link.springer.com.