Luspatercept's Impact on Low-Risk MDS: A Shift in Treatment Strategy

In an interview, Guillermo Garcia-Manero, MD, discusses the impact luspatercept (Reblozyl) has had on the treatment landscape for myelodysplastic syndromes (MDS).

Luspatercept is changing how doctors think about treating low-risk MDS. Traditionally, the goal has been to manage symptoms and improve a patient’s quality of life. However, recent findings suggest that luspatercept may do more than that—it could be extending a patient's life.

In clinical trials, it took around 36 months for a survival difference to appear between patients treated with luspatercept and those on older, standard-of-care drugs. This delay is expected because low-risk MDS progresses slowly, but the long-term data shows that luspatercept improves survival over time. This suggests that the drug is doing more than just raising hemoglobin levels and reducing the need for blood transfusions; it may be changing the disease’s underlying biology, possibly by modulating the TGF-beta protein and affecting other organs like the heart and lungs. While more research is needed to understand the exact mechanism, this survival data is a significant finding that could fundamentally change treatment goals for MDS from purely symptomatic to survival-focused.

These findings are particularly important for the two-thirds of patients who present with low-risk MDS. In the past, these patients may not have been treated as aggressively, but now, with a treatment that improves survival and has a safety profile similar to older drugs, physicians may start thinking about promoting longer survival as a primary goal. Dr Garcia-Manero points out that there were no new safety signals or long-term concerns with luspatercept; in fact, there was even a lower rate of transformation to high-risk MDS.

This data will likely empower doctors in their conversations with patients, as they can now offer a newer, more effective option that potentially extends life. While acknowledging that there's still a need for better quality-of-life measurements and that the survival data was a secondary endpoint, the speaker ultimately believes that these findings will encourage clinicians to adopt luspatercept more widely. Looking ahead, the next step will be to explore rational combination therapies to further increase response rates and improve patient outcomes.