High-Risk MDS Patients Starve for Lifesaving Treatment

Underuse of Key Drugs Trails Recommendations, Widens Health Disparities

A significant portion of patients diagnosed with high-risk myelodysplastic syndromes (MDS) are not receiving recommended hypomethylating agents (HMAs), according to a major study. This underutilization of life-extending therapies may explain why outcomes for MDS patients have stagnated over the last two decades, despite the availability of these crucial medications.

Treatment Gaps Revealed

The analysis, the largest of its kind in the U.S., highlights that nearly half of patients who should be initiated on HMAs are not. Even among those who start treatment, many do not complete the full course. Strikingly, women and non-white individuals are significantly less likely to receive HMAs compared to white males.

“The disparities we found based on gender, race, and ethnicity were really striking. 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.”

—Sudipto Mukherjee, MD, PhD, MPH, study’s lead author and physician in hematology and medical oncology at Cleveland Clinic

Understanding MDS and HMAs

MDS is a group of bone marrow cancers where the body fails to produce sufficient healthy blood cells. This often leads to severe fatigue and increased risks of infection and bleeding. Without intervention, the disease can progress to acute myeloid leukemia. For older adults over 70, who often cannot undergo bone marrow transplants—the only cure—due to health complications or cost, HMAs represent the primary treatment option.

Real-World Treatment Lags

HMAs function by altering genes involved in blood cell production, thereby increasing healthy blood cell output and slowing MDS progression. While clinical trials demonstrate HMAs’ ability to extend lives and improve quality of life, real-world data shows minimal progress since the FDA approved azacitidine and decitabine nearly 20 years ago. Researchers examined Medicare claims for over 49,000 U.S. adults, assessing HMA administration against established guidelines and factoring in clinical, demographic, and socioeconomic variables.

The findings indicated that only 16% of newly diagnosed MDS patients on Medicare received HMAs between 2011 and 2014. This figure is roughly half of the estimated 30-40% of patients who are classified as high-risk at diagnosis and for whom HMAs are recommended. Notably, patients over 85, women, and non-white individuals were less likely to begin HMA treatment. Women were 19% less likely, Black patients 30% less likely, and patients of other races 22% less likely to start HMAs compared to white patients. While the lower uptake in the very elderly might be attributed to treatment refusal, no clear reason was found for the disparities based on gender and race, suggesting potential implicit bias.

Treatment Duration a Critical Barrier

Optimal HMA outcomes depend on correct dosing and duration, with best responses typically seen after four to six monthly cycles. However, the study revealed that most patients did not adhere to recommended treatment lengths. Over a third stopped by the fourth cycle, and half by the sixth. Fewer than half (30-40%) received the full guideline-directed dose 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. 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.”

—Dr. Mukherjee

Dr. Mukherjee explained that initial decreases in blood cell counts, leading to increased fatigue and transfusion needs, are normal during the early stages of HMA therapy. He suggested that physicians and patients might be too quick to adjust or halt treatment in response to these temporary effects. Such decisions, especially when patients lack robust support systems or easy access to care, can significantly limit the medications’ benefits.

Bridging the Treatment Gap

One proposed solution involves community health clinics collaborating with larger tertiary care centers. This partnership could provide patients with initial HMA treatment consultations at specialized hospitals, followed by ongoing care managed by local clinics under expert guidance. This model aims to ensure adherence to recommended treatment plans and facilitate management of side effects or dosage adjustments as needed.

The study’s reliance on Medicare claims data, while providing a large, nationally representative cohort of older adults with high MDS prevalence, meant researchers lacked access to specific disease markers to fully assess treatment appropriateness. Additionally, the data did not detail the exact reasons for early treatment discontinuation.

The U.S. Preventive Services Task Force recommends regular screenings for colorectal cancer in adults aged 45 to 75. Early detection and treatment are crucial for improving survival rates in many cancers, mirroring the importance of consistent HMA therapy for high-risk MDS patients.