Effective Therapy for MDS is Vastly Underused

Over half of eligible patients do not receive recommended therapies or complete the full course of treatment; white males are most likely to get the right treatment at the right dose

(WASHINGTON – August 6, 2025) – Most patients with high-risk myelodysplastic syndromes (MDS) do not receive guideline-recommended treatment with hypomethylating agents (HMAs), according to results published in Blood Neoplasia. The findings suggest that underuse of these drugs may help explain why MDS outcomes have not improved over the past two decades when these life-extending medications became available.

The study is the largest analysis of MDS treatment patterns in the United States to date and the most comprehensive study of real-world use of HMAs, which are highly effective in improving outcomes. HMAs are the best available treatment option for the majority of older people with high-risk disease who cannot get a curative bone marrow transplant. According to the study findings, about half of patients who should be started on an HMA are not receiving these drugs, and even among those who do start treatment, many do not complete the recommended therapy. The results also showed that women and non-white patients were significantly less likely to receive the treatment than white males.

“The disparities we found based on gender, race, and ethnicity were really striking,” said the study’s lead author, Sudipto Mukherjee, MD, PhD, MPH, a physician in the department of hematology and medical oncology at Cleveland Clinic. “Given the absence of newly approved therapies over the last two decades, the most impactful way to improve outcomes in newly diagnosed high-risk MDS requires that we do better with the available therapies. Making changes with these therapies and how they are given (that is, when to treat and how to treat) is a key intervention that can have a huge impact.”

MDS, a group of blood cancers in which the bone marrow does not produce enough healthy blood cells, causes debilitating fatigue and increased susceptibility to infections and bleeding. Without treatment, MDS can progress to acute myeloid leukemia. MDS is most common in adults over the age of 70, most of whom cannot get a bone marrow transplant – the only known cure for MDS – due to frailty, comorbidities, or cost.

HMAs modify the genes involved in blood formation in a way that boosts the production of healthy blood cells and slows the progression of MDS. Although these drugs do not cure the disease, clinical trials have shown that they help patients live longer and improve quality of life. However, real-world outcomes have shown little improvement since the U.S. Food and Drug Administration approved two HMAs, azacitidine and decitabine, for high-risk MDS about 20 years ago.

The researchers analyzed Medicare claims data from more than 49,000 U.S. adults to assess which patients received HMAs and whether the drugs were being administered according to guidelines. They assessed clinical factors such as blood counts, transfusions, frailty, and comorbidities, as well as demographic factors such as population density, neighborhood education and poverty levels, and the concentration of physicians and specialists where patients live.

According to the findings, just 16% of newly diagnosed patients with MDS on Medicare received HMAs during the period analyzed (2011-2014). This is about half of the estimated 30-40% of patients who fall into the high-risk category at the time of diagnosis for which HMAs are recommended. People who were older than 85, female, or non-white were significantly less likely to start HMA treatment. Although men and women are diagnosed with MDS at roughly the same rate, the study found women were 19% less likely to start HMAs. Black patients were 30% less likely to start HMAs, and patients of other races were 22% less likely to start HMAs compared to white patients.

Researchers suggested that the lower rate of HMA uptake among people over age 85 may be explained by a tendency for older patients to decline treatment. However, they could not identify any obvious reason why women or non-white patients would be less likely to receive the treatment, suggesting that implicit bias may be a factor.

The dosing and duration of treatment strongly influence HMA outcomes, with the best response to treatment typically achieved after four to six one-month cycles. However, the study revealed that most patients who received HMAs did not complete the treatment as recommended. Over one-third of patients discontinued the treatment by the end of the fourth cycle, and half discontinued by the end of the sixth cycle. Fewer than half (30-40%) received the full guideline-directed dose of their drug in each of the first four cycles.

“If you are not even treating the patients for the recommended duration of time, you will not see a response,” said Dr. Mukherjee. “When starting these treatments, blood counts and transfusion needs may initially get worse before they improve, and you have to plow through it. That is not the time to discontinue, but that is what the data is saying.”

It is normal for patients’ blood cell counts to decrease in the first few cycles of HMA treatment, which can lead to increased fatigue and a greater need for blood transfusions. Based on the data, Dr. Mukherjee suggested that doctors and patients may be too quick to skip doses or stop treatment in response to these effects. While this can be understandable in cases where patients have less support, or access to care, or are in poorer health overall, failing to deliver the full course of treatment as recommended undermines patients’ ability to fully benefit from these medications.

One way to address this gap could be for community health clinics to partner with larger tertiary care centers to guide HMA treatment, Dr. Mukherjee suggested. For example, patients could visit a hospital with more expertise in HMA treatment for a one-time consultation to formulate a treatment plan, and then return to their local community clinic where doctors would follow through on that recommended course of treatment, referring back to the tertiary care center as needed for guidance on handling side effects or altering the dosage.

As the study was a retrospective analysis based on Medicare claims data, the researchers noted that they did not have access to data on disease markers necessary to comprehensively assess the appropriateness of the decision of whether or not to start HMA treatment in all patients, nor did the data specify why HMA treatment was stopped early in each case. Despite these limitations, using Medicare claims data provided a large, nationally representative study cohort in older adults, a demographic with the highest prevalence of MDS.

Blood Neoplasia (www.bloodneoplasia.org) is an online only, open access journal of the American Society of Hematology (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.

Contact:
Claire Whetzel, 202-629-5085
cwhetzel@hematology.org