Posted: Tuesday, March 9, 2021
A group led by Qifa Liu, MD, of the Southern Medical University in Guangzhou, China, and a colleague published a mini-review of targeted drugs used as maintenance therapy in patients with acute myeloid leukemia (AML) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Their findings, published in the Journal of Hematology & Oncology, discussed the use of hypomethylating agents, FLT3 inhibitors, isocitrate dehydrogenase inhibitors, venetoclax, histone deacetylase and Hedgehog inhibitors, and immunotherapies.
Hypomethylating agents have shown favorable efficacy and tolerability in patients with AML; however, some studies suggest that patients may not benefit from maintenance treatment with hypomethylating agents. Relapse rates across various studies vary between about 16% and 53%. FLT3 inhibitors have been explored in patients both with and without FLT3 mutations. There is growing evidence to suggest that patients with mutations in FLT3 may benefit from the use of FLT3 inhibitors after allo-HSCT. Further research is necessary to assess which specific FLT3 inhibitors are most effective in patients with AML.
Because about 20% of AML genomes have mutations in isocitrate dehydrogenase, isocitrate dehydrogenase inhibitors are under study in AML. There is an ongoing phase I trial evaluating the safety of an isocitrate dehydrogenase inhibitor in the maintenance phase following HSCT. Venetoclax has also been demonstrated to be effective and tolerable in patients with AML and is safe in the maintenance phase.
Histone deacetylase inhibitors have been shown to induce cell-cycle arrest, cell differentiation, and AML cells' apoptosis. These drugs have demonstrated favorable survival outcomes when used after HSCT in the maintenance phase. Similarly, a Hedgehog pathway inhibitor showed a favorable benefit-risk profile for patients with AML. Ongoing trials will further assess the use of Hedgehog inhibitors as maintenance for patients undergoing stem cell transplants.
Traditional immunotherapies, including lymphocyte infusion, interleukin-2, and interleukin-alpha, may prevent relapse in patients with AML after stem cell transplant. However, further data are needed. Chimeric antigen receptor T-cell therapy, antibody-directed therapy, immune checkpoint inhibitors, and vaccines are all under investigation in this patient population as well.
Disclosure: The authors reported no conflicts of interest.