Future Perspectives in LR-MDS: Addressing Unmet Clinical Needs and Treatment Challenges

We are definitely in a better place now with new treatment options like luspatercept and even imetelstat available for patients. These therapies offer hope beyond the traditional erythropoiesis-stimulating agents, which fail in a significant portion of patients—close to 70%—with response durations typically ranging from 20 to 30 months. Having additional options is valuable for improving lab values and quality of life, but it’s important to recognize that patients eventually stop responding, highlighting the ongoing need for novel therapeutics.

There is considerable variability in patient responses as well. Some individuals experience robust hemoglobin increases of more than 1.5 g/dL, while others may not achieve meaningful improvement. This variability, in part, may relate to mutational burden, as patients with higher mutation loads tend to respond less effectively. Understanding these genetic factors better could guide more personalized therapy choices in the future and help identify additional effective treatments.

Although low-risk disease patients generally have long survival times, disease progression remains a concern. Developing agents that modify disease state and potentially improve overall survival would be a major advancement. Early data with luspatercept hints at a survival benefit, but confirmation requires more evidence. Meanwhile, the pursuit of new drugs that might alter disease progression is essential to improve outcomes for this patient population.