Debate: Sequencing Therapies for LR-MDS: ESA First vs Luspatercept First
Panelists discuss the sequencing of therapies in lower-risk myelodysplastic syndromes, debating whether to initiate treatment with erythropoiesis-stimulating agents due to cost and patient variability or with luspatercept for its superior efficacy and potential disease-modifying effects, while highlighting ongoing trials exploring combined or sequential strategies.
The discussion focused on sequencing therapies for lower-risk myelodysplastic syndromes (MDS), specifically whether erythropoiesis-stimulating agents (ESAs) or luspatercept should be used first. One perspective highlighted that while clinical trials demonstrated luspatercept’s superiority over ESAs in certain patient groups, real-world experience sometimes shows a different patient distribution, with more SF3B1 mutation–negative cases than positive ones. For those patients, the difference in response rates between luspatercept and ESAs is less pronounced, suggesting ESAs might still be a reasonable first choice. Additionally, starting with ESAs allows for the possibility of using luspatercept later if the patient does not respond. Cost considerations also support the initial use of ESAs, which tend to be less expensive than luspatercept.
In contrast, another viewpoint argued for luspatercept as the preferred first-line therapy due to its higher effectiveness and durability. Data from recent trials indicated that ESAs often have a high failure rate, particularly in patients with elevated serum EPO levels. Subgroup analyses from these studies showed that patients naive to ESAs tended to respond better to luspatercept. Further survival data suggested a trend toward improved overall survival with luspatercept, implying a potential disease-modifying effect. This evidence supports the idea that luspatercept might change the disease biology more effectively than ESAs, making it a stronger candidate for initial therapy.
Ultimately, the debate may be resolved by ongoing combination trials exploring the sequential or combined use of both agents. Early findings raise the possibility that using ESAs to stimulate early-stage erythroid maturation followed by luspatercept for later-stage maturation could yield synergistic benefits. Until these results are available, treatment sequencing will depend on clinical judgment, patient characteristics, and economic factors, making personalized approaches essential in managing lower-risk MDS.
Newsletter
Stay up to date on recent advances in the multidisciplinary approach to cancer.
