Discussion
toxicity, sideroblasts
In the MEDALIST study, luspatercept demonstrated a consistent benefit in reducing RBC transfusion burden within the first 24 weeks of treatment among patients with LR-MDS [The findings of this analysis have value in the real-world clinical setting where luspatercept can lower transfusion burden and continue to offer clinical benefits beyond 25 weeks of treatment. This analysis has revealed a lower cumulative transfusion burden in terms of the number of RBC transfusion units and visits with continued luspatercept treatment and has shown that transfusion burden among initial luspatercept nonresponders can be improved by extending treatment. Continued luspatercept treatment beyond 25 weeks may provide RBC-TI and hemoglobin improvement for patients who require additional time to achieve a response indicative of clinical benefit.Achieving transfusion independence in LR-MDS is an important treatment goal given the negative impact of RBC transfusions on OS and leukemia-free survival in patients with LR-MDS [According to the package insert, treatment with luspatercept should be discontinued if a patient does not experience a decrease in transfusion burden after 9 weeks of treatment at the maximum dose level or in cases of unacceptable toxicity [A strength of this analysis is that the patient-level data were obtained from a large multinational phase 3 randomized, placebo-controlled trial. Limitations include its nature as a post hoc analysis focused on a subgroup of patients not attaining a response, resulting in the loss of statistical inference attainable from a randomized population. Therefore, these results should be confirmed in future prospective analyses [In conclusion, our findings suggest that continuing luspatercept treatment beyond 25 weeks may provide clinical benefit for a meaningful proportion of patients with LR-MDS with ring sideroblasts who otherwise have limited treatment options. These findings may inform clinical practice treatment decisions with regard to the timing of clinical benefit, the relevance of increasing the dose level of luspatercept in the absence of an initial response, and the consideration of luspatercept treatment for patients with high or low pretreatment RBC transfusion burden to facilitate a rational identification of the patients most likely to benefit.