Combinations of hypomethylating agents (HMAs, especially with immune checkpoint inhibitors, have shown promising signals in both the frontline and HMA-refractory setting.

Several other novel agents including orally available and longer acting HMAs, the BCL-2 inhibitor venetoclax, oral agents targeting driver mutations (IDH1 and IDH2, FLT3), immunotherapies and new options for intensive chemotherapy are being studied in clinical trials (Bewersdorf et al. 2020). Examples of non-chemotherapy approaches include therapy targeting marrow microenvironment and immune checkpoints such as TIM-3 and antiCD47 monoclonal antibody-magrolimab.

Examples of new treatments for adults with MDS, approved by the America’s Food and Drug Administration, include luspatercept (Reblozyl) for lower risk MDS and the oral combination of decitabine and cedazuridine (Inqovi) for higher risk MDS (Harris 2020).

Clinical trials for MDS may be available, especially in those with higher risk disease, and they may also be eligible for AML trials. Refer to section 4.4 for clinical trial resources.

The key principle for precision medicine is prompt and clinically oriented communication and coordination with an accredited laboratory and pathologist. Tissue analysis is integral for access to emerging therapies and, as such, tissue specimens should be treated carefully to enable additional histopathological or molecular diagnostic tests in certain scenarios.