Debate Round 2: Managing Luspatercept Super Responders (Dose Reduce vs Hold Dose)

Debate Round 2: Managing Luspatercept Super Responders (Dose Reduce vs Hold Dose)

A key issue in managing patients who achieve hemoglobin levels above 12 g/dL on luspatercept is whether to reduce the dose or hold treatment altogether. Clinicians emphasize that the primary goal in lower-risk MDS is improving quality of life and maintaining transfusion independence, while minimizing risks. Dose reduction strategies—either lowering the administered amount or extending the interval between doses—are sometimes preferred to prevent the fluctuations in hemoglobin that can negatively impact patients’ ability to plan daily activities or travel. However, long-term safety data are still needed, especially to better understand the impact of prolonged higher hemoglobin levels on cardiovascular events.

Others argue in favor of holding the dose in super responders, citing both safety concerns and cost. While higher hemoglobin levels generally improve energy and functionality, there are no robust data on the risks of hemoglobin rising beyond 14 or 16 g/dL in this population. Additionally, given the high cost of luspatercept, allowing patients to sustain hemoglobin levels for several months without ongoing dosing could reduce both financial burden and treatment intensity. This approach mirrors real-world scenarios where patients may naturally extend dosing intervals around holidays or scheduling conflicts, often without compromising outcomes.

Practical considerations also emerge. Some clinicians note that while luspatercept is a subcutaneous injection, US health care regulations and pharmacy practices currently limit its use in the home setting, unlike insulin or GLP-1 agonists. This restriction adds to treatment burden, requiring patients to travel to infusion centers. Panelists express frustration at these systemic limitations, noting that greater flexibility—such as allowing home administration or tailored dosing intervals—could significantly improve patient quality of life. Overall, the debate highlights a balance between maintaining efficacy, ensuring safety, reducing costs, and adapting treatment to the realities of patient lifestyles.