Why Patients With MDS Aren't Living Longer on Approved Drugs

In an interview with Targeted Oncology, Sudipto Mukherjee, MD, PhD, MPH, Leukemia Program, Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, discusses the rationale behind a recent study published in Blood Neoplasia investigating disparities in real-world treatment patterns of hypomethylating agents (HMAs) among patients with myelodysplastic syndromes (MDS) in the US.

The rationale behind this study was observations from several studies conducted by investigators across the country over the past few years. These studies showed that the 2 drugs approved for newly diagnosed high-risk MDS, the HMAs azacitidine and decitabine, were approved by the FDA in 2004 and 2006, respectively.

Given that these drugs have been approved and used for 2 decades, most would expect to see significant survival benefits. However, most studies that have examined the survival of these MDS patients over the past 20 years show very little to, at most, a very modest improvement in survival. This doesn't add up and fails to replicate the extent of the benefit seen in the original clinical trial. This discrepancy led investigators to think about what the reason might be for not seeing the expected improvement.

Mukherjee also notes that for these newly diagnosed patients with high-risk MDS, the only known therapeutic modality with curative potential is an allogeneic bone marrow transplant. However, in the US, these patients are typically 70 years or older by the time they are diagnosed. Unfortunately, more than half of them have significant other medical conditions or comorbidities, which are severe enough to disqualify them from being bone marrow transplant candidates. Therefore, the majority of them will never be able to proceed with a bone marrow transplant. For them, the only options are these 2 drugs approved 2 decades ago. Mukherjee believes the field can do better than what we are currently seeing in the population-level survival data.

This led investigators to take a deeper dive and find out how these patients are being treated, who is being treated, and whether they are being treated according to the recommended guidelines. They also tried to look at factors beyond clinical ones that might be preventing people from getting treated in a timely manner or causing them to prematurely stop treatment.

With these questions in mind, investigators designed this study. They gathered clinical data using a claims database and linked it with demographic data, treatment data, and county-level characteristics. They looked at the rural-urban continuum, the population size of the regions where MDS cases were reported, the educational level (specifically, how many people had at least a high school diploma), the percentage of people living below the federal poverty level, and the number of doctors per 100,000 people in that region.

The goal was to get a truly comprehensive assessment of both clinical and non-clinical factors, including demographic and socioeconomic factors, to try to answer these questions. Investigators wanted to see if they could find any answers that could become targets for intervention to improve patient outcomes.

This description was generated with assistance from Google Gemini. It was edited and reviewed by Targeted Oncology staff. If you have any questions about the use of AI, please contact us.

REFERENCE:

Mukherjee S, Dong W, Gerds AT, et al. Disparities in Real-World Treatment Patterns of Hypomethylating Agents Among Patients with Myelodysplastic Syndromes in the US. Blood Neoplasia 2025; 100156. doi: https://doi.org/10.1016/j.bneo.2025.100156