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Home NEWS Science News Cancer

Effective MDS Therapy Remains Underutilized, Particularly Among Women and Non-White Patients

Bioengineer by Bioengineer
August 6, 2025
in Cancer
Reading Time: 4 mins read
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(WASHINGTON – August 6, 2025) – A striking new study has unveiled a troubling reality in the treatment landscape of high-risk myelodysplastic syndromes (MDS) in the United States: the underutilization of guideline-recommended hypomethylating agents (HMAs) remains a pervasive problem two decades after their approval. Despite clear evidence that HMAs, including azacitidine and decitabine, can meaningfully extend survival and improve quality of life for patients with MDS, real-world clinical outcomes have stagnated. This discrepancy points towards significant gaps in care delivery that could be driving persistently poor prognoses for this vulnerable population.

Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, manifesting as cytopenias and an increased risk of transformation to acute myeloid leukemia (AML). The bone marrow’s failure to generate adequate healthy blood cells causes patients profound fatigue, vulnerability to infections due to neutropenia, and bleeding complications from thrombocytopenia. Although the only curative option is an allogeneic bone marrow transplant, most patients with MDS—often elderly and with comorbidities—are ineligible for transplantation, which elevates the importance of effective medical therapies like HMAs.

This largest-to-date analysis of MDS treatment patterns, recently published in Blood Neoplasia, assessed Medicare claims data from more than 49,000 adults to evaluate the real-world usage of azacitidine and decitabine between 2011 and 2014. The results highlighted a stark underuse of these life-extending agents: only 16% of newly diagnosed patients received HMAs, while clinical guidelines recommend treatment in approximately 30-40% of patients classified as high-risk at diagnosis. The study paints a concerning picture of missed therapeutic opportunities in a disease with otherwise limited treatments.

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One of the study’s most distressing revelations was the stark disparity in treatment initiation across demographic groups. Women and non-white patients were significantly less likely to receive HMAs compared to white males. Specifically, women were found to be 19% less likely to start therapy, Black patients 30% less likely, and patients of other racial backgrounds 22% less likely. These findings underscore systemic inequities in cancer care delivery and raise important questions about implicit bias, healthcare access, and the sociocultural factors that influence treatment decisions.

Age also played a critical role in treatment patterns. Patients over the age of 85 were markedly less likely to initiate HMA therapy. While this may partially be attributed to patient or provider treatment preference considering frailty or comorbid conditions, the authors could not conclusively explain the gender and race disparities, suggesting underlying biases or structural barriers in care provision might be influential. Such disparities could compound already poor outcomes, warranting urgent attention from clinicians and policymakers alike.

Adding complexity to the issue, adherence to treatment regimen recommendations was also suboptimal. The efficacious response to HMAs typically requires sustained treatment over four to six consecutive one-month cycles. However, the study found that over one-third of patients discontinued therapy before completing the fourth cycle, and a full half stopped before the sixth. Remarkably, less than half of patients received the full guideline-recommended dose during the initial treatment cycles, signaling that many patients are either underdosed or prematurely taken off therapy.

This incomplete treatment adherence is particularly alarming because the pharmacodynamics of HMAs involve an initial period where blood cell counts may paradoxically decline before improvement occurs. Early side effects like cytopenias can exacerbate fatigue and increase transfusion needs, potentially leading clinicians or patients to prematurely discontinue therapy due to these transient toxicities. However, discontinuing before adequate cycles are completed substantially undermines therapeutic benefits and reduces the likelihood of favorable clinical outcomes.

Study lead author Dr. Sudipto Mukherjee of the Cleveland Clinic emphasized that persevering through early treatment challenges is crucial. He noted that transient worsening of blood counts is a predictable, manageable phase in the drug’s mechanism of action, not a sign of treatment failure. This insight highlights the necessity for better patient education and closer clinical monitoring to support patients through the difficult initiation phase, reinforcing the need for adherence to predetermined regimen durations and dosing.

Beyond individual patient dynamics, the researchers examined systemic and environmental factors affecting treatment access and delivery. Variables such as population density, neighborhood education level, poverty rates, and local concentrations of physicians and specialists were considered. These broader social determinants of health likely contribute to the observed disparities and underscore the complex interplay between biology, social environment, and healthcare infrastructure in MDS management.

Addressing the treatment gaps identified, Dr. Mukherjee proposed innovative collaborative care models. One promising approach involves partnerships between community health clinics and tertiary care centers specializing in MDS and HMA therapy. Such a strategy would enable patients in localized settings to receive expert treatment planning and ongoing management guidance, potentially improving adherence, managing side effects more competently, and ensuring better patient outcomes without necessitating frequent travel to large centers.

While this study offers pivotal insights, the authors acknowledge its limitations. Reliance on retrospective Medicare claims data means that granular clinical parameters, such as molecular disease markers, were not available. This limited the ability to definitively determine clinical appropriateness behind treatment decisions or reasons for early therapy discontinuation. Nonetheless, Medicare data afford a large, demographically representative cohort of older adults—the population most burdened by MDS—lending significant weight to the study’s conclusions.

The persistence of underuse and early discontinuation of HMAs does more than represent a missed opportunity; it may partly explain why MDS outcomes have remained largely unchanged despite two decades of available effective therapy. By controlling the disease’s progression and improving hematopoiesis, HMAs offer a means to enhance patient survival and quality of life in a population often too frail for curative interventions. Closing this treatment gap thus represents a critical frontier in hematologic oncology.

As the population ages and MDS prevalence rises, reexamining real-world treatment patterns and disparities assumes heightened urgency. Interventions ranging from increasing provider and patient education to structural changes in care delivery models hold promise to overcome the barriers illuminated by this landmark study. Ultimately, ensuring that every eligible patient has timely and sustained access to HMAs may be the most potent tool to alter the natural history of high-risk MDS for the better.

Subject of Research: Treatment utilization and disparities in high-risk myelodysplastic syndromes

Article Title: Underuse of guideline-recommended hypomethylating agents in high-risk myelodysplastic syndromes: a nationwide analysis

News Publication Date: August 6, 2025

Web References: https://doi.org/10.1016/j.bneo.2025.000582, https://ashpublications.org/bloodneoplasia, https://www.hematology.org/

Keywords: Hematology, Blood cancer, Oncology, Health disparity, Health care delivery

Tags: azacitidine and decitabine effectivenessbarriers to MDS treatment accessdisparities in cancer treatmenthematopoietic disorders treatment gapshigh-risk myelodysplastic syndromeshypomethylating agents for MDSimproving quality of life in MDS patientsMDS therapy underutilizationMedicare claims data analysis MDSnon-White patients and MDSreal-world clinical outcomes in MDSwomen and MDS treatment

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