Treatment Options for Myelodysplastic Syndromes in Older Adults
Myelodysplastic syndromes (MDS) are a group of diverse bone marrow disorders commonly affecting older adults, characterized by ineffective blood cell production and an increased risk of progression to acute myeloid leukemia (AML). The treatment approach varies significantly based on disease risk category, patient age, overall health status, and specific clinical manifestations. Since MDS primarily impacts elderly individuals, therapeutic strategies must balance efficacy with tolerability, especially considering comorbidities and reduced physiological reserves.
Understanding the Dual Nature of MDS
MDS is defined by two major clinical outcomes: bone marrow failure and the potential for leukemic transformation. Bone marrow failure leads to low blood counts—resulting in anemia, infections, and bleeding—while high-risk forms carry a substantial chance of evolving into AML. Accurate risk stratification using tools like the Revised International Prognostic Scoring System (IPSS-R) is essential to guide therapy decisions and predict outcomes.
Managing Low-Risk MDS: Supportive Care and Immune Modulation
For patients with lower-risk disease, the primary goal is symptom management and improving quality of life. Supportive care remains a cornerstone, including regular red blood cell and platelet transfusions for those with severe cytopenias. To reduce transfusion dependence, hematopoietic growth factors such as erythropoiesis-stimulating agents (ESAs) and granulocyte colony-stimulating factor (G-CSF) are frequently used.
In certain subgroups, particularly younger patients with hypocellular bone marrow and evidence of immune-mediated suppression, immunosuppressive therapy can be effective. Agents like antithymocyte globulin (ATG) and cyclosporine have shown response rates in selected cases. Additionally, lenalidomide has proven highly beneficial for patients with the 5q deletion subtype, significantly reducing transfusion needs and inducing cytogenetic remissions.
The Role of Emerging Therapies in Early-Stage Disease
Recent advances have introduced novel agents targeting specific molecular pathways. Luspatercept, a first-in-class erythroid maturation agent, has demonstrated impressive results in reducing red cell transfusion burden among patients with ring sideroblast-positive MDS. This drug works by promoting late-stage red blood cell development, offering a new dimension in managing chronic anemia.
Treating High-Risk MDS in Elderly Patients
High-risk MDS poses a greater challenge due to its aggressive nature and higher likelihood of transforming into leukemia. Allogeneic stem cell transplantation remains the only potentially curative option; however, it is typically reserved for younger, fit patients. Given that most individuals diagnosed with MDS are over 60 or even 70 years old, transplant eligibility is limited by age and comorbid conditions.
For these older adults, hypomethylating agents (HMAs) such as azacitidine and decitabine form the backbone of treatment. These drugs work by reversing abnormal DNA methylation patterns that silence tumor suppressor genes. Clinical trials have shown HMAs can delay disease progression, reduce blast counts, and improve survival compared to supportive care alone.
Innovative Combination Strategies on the Rise
In recent years, combination therapies have gained momentum, offering enhanced responses over monotherapy. Promising approaches include pairing hypomethylating agents with targeted drugs such as Bcl-2 inhibitors (e.g., venetoclax), which promote cancer cell apoptosis. Early-phase studies show higher response rates when venetoclax is added to azacitidine, especially in patients with poor prognostic features.
Another area of active investigation involves combining HMAs with immune checkpoint inhibitors like PD-1 antibodies. While still experimental and requiring careful monitoring for immune-related adverse events, this strategy aims to unleash the body's immune system against malignant clones. Additionally, all-trans retinoic acid (ATRA), traditionally used in acute promyelocytic leukemia, is being explored in combination regimens for its differentiation-inducing properties.
Personalized Medicine and Future Directions
As genomic profiling becomes more accessible, treatment is increasingly tailored to individual mutations—such as TP53, SF3B1, or ASXL1—which influence prognosis and response to therapy. Ongoing clinical trials continue to evaluate novel combinations, minimal residual disease monitoring, and maintenance strategies post-response.
Ultimately, managing MDS in older adults requires a multidisciplinary approach that integrates disease biology, patient preferences, and functional status. With rapid advancements in targeted and immunomodulatory therapies, the outlook for elderly patients with MDS continues to improve, offering hope for longer, higher-quality lives.