Dr Komrokji on Unanswered Questions in High-Risk MDS Management

"High-risk MDS obviously remains a very challenging area of unmet need…and there are a lot of gaps that could be addressed by a consensus."

Rami Komrokji, MD, the vice chair of the Malignant Hematology Department and a senior member of the Malignant Hematology and Experimental Therpaeutics Program at Moffitt Cancer Center; as well as a professor of medicine & oncologic sciences in the College of Medicine at the University of South Florida, discusses the need for consensus guidelines regarding the management of high-risk myelodysplastic syndromes (MDS), as highlighted in a discussion at the 2025 OncLive® Bridging The Gaps: Leukemia, Lymphoma, and Multiple Myeloma Meeting.

High-risk MDS remains an area of significant unmet need, with the disease having a substantial effect on short-term survival, Komrojki begins. Allogeneic stem cell transplantation is considered the only potentially curative option for these patients, and its utilization has expanded with improvements in donor availability and increased eligibility among older patients, he says. However, advancements in the management of high-risk MDS has been hindered by multiple negative randomized clinical trials, leaving hypomethylating agents (HMAs) as the primary standard of care (SOC), Komrokji states.

Several critical gaps remain in the management of high-risk MDS that require consensus, Komrokji continues. Key questions include determining the optimal timing of transplantation, whether pretransplant treatment is necessary, and whether to incorporate approaches from acute myeloid leukemia (AML) management into MDS treatment paradigms, he outlines, adding that venetoclax (Venclexta) has become a SOC in AML, but its role in high-risk MDS is still under investigation. The evolving classifications of MDS and AML, such as the International Consensus Classification (ICC), which now designates cases with at least 10% blasts as MDS/AML, further blur the distinction between these diseases and create uncertainty regarding treatment strategies, Komrokji notes.

Additional challenges include determining treatment strategies for patients ineligible for transplant, defining appropriate continuation and monitoring strategies for HMAs, and identifying next steps if patients progress on these agents—an inevitable outcome for many patients, Komrokji emphasizes. Repeating molecular testing in relapsed or refractory disease is crucial, as newly emerging targets may present opportunities for novel therapies, he says. Consensus guidelines based on the best available evidence are needed to standardize management approaches in these areas, and ongoing clinical trials are exploring strategies that may shift the current MDS SOC beyond HMAs, Komrokji concludes.