Debate: Optimal Initiation of ESAs, Luspatercept, and Imetelstat: Pretransfusion vs Posttransfusion
Panelists discuss the debate on optimal timing for initiating therapies in lower-risk myelodysplastic syndromes, balancing early intervention to improve quality of life and prevent complications against a conservative approach favoring treatment initiation upon transfusion dependency or symptom onset.
The debate focused on the optimal timing to initiate treatments like erythropoiesis-stimulating agents, luspatercept, and imetelstat in lower-risk patients with myelodysplastic syndrome (MDS), particularly around transfusion dependency. One side argued for earlier initiation before patients become heavily transfusion dependent, emphasizing that anemia is the main concern in lower-risk MDS where cure is unlikely but quality of life improvement is critical. Early treatment was presented as a way to prevent transfusion complications and preserve cardiac reserve, especially in patients with preexisting cardiac issues. Data suggesting earlier therapy leads to better durable responses and potentially improved survival supported the argument to start treatment before a high transfusion burden develops.
The opposing view favored a more conservative approach, recommending therapy initiation only after patients become transfusion dependent or symptomatic. This position highlighted the economic and logistical burdens of premature treatment and the lack of randomized data supporting early intervention in non–transfusion-dependent patients. It was argued that observing patients’ response to transfusions first provides useful clinical information and helps avoid unnecessary exposure to treatment. Additionally, variability in hemoglobin levels and symptom perception among patients means individualized timing remains important.
The discussion concluded with general agreement that treatment should be patient centered, initiated when symptoms or hemoglobin decline warrant intervention, rather than strictly by laboratory thresholds alone. There was also debate on appropriate end points for transfusion independence duration in clinical trials, with consensus that 16 weeks is a reasonable standard for meaningful clinical benefit. The moderator summarized the debate by endorsing the idea that “the best transfusion is no transfusion,” highlighting the shared goal of minimizing transfusion burden and improving quality of life in MDS patients.
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