Frontline Treatment for Newly Diagnosed Lower-Risk Myelodysplastic Syndromes (LR-MDS)

Following a recent update in to NCCN gGuidelines, Drs. Garcia- Manero and Swoboda introduce themselves and theirwill discussion about the changing landscape of lower-risk myelodysplastic syndromeLR-MDS treatment.

Panelists discuss how the initial presentation of lower-risk myelodysplastic syndromes (LR-MDS) involves anemia and other cytopenias, with updates on MDS risk assessment using prognostic scoring systems like such as IPSS-R and IPSS-M to guide treatment decisions.

Panelists discuss how the NCCN Guidelines define lower-risk myelodysplastic syndrome (LR-MDS) based on clinical hallmarks such as anemia and cytopenias, with treatment decisions guided by prognostic scoring systems (IPSS-R, IPSS-M), and how real-world data supports the evolving first-line treatment landscape for LR-MDS, including the use of therapies such as luspatercept.

Panelists discuss how frontline luspatercept is emerging as an effective treatment for anemia in lower-risk myelodysplastic syndrome (LR-MDS), demonstrating significant improvements in hemoglobin levels and transfusion independence, as supported by clinical trial data.

Panelists discuss how the final efficacy and safety analysis from the COMMANDS trial (Della Porta et al, Lancet 2024) highlights the role of luspatercept in first-line treatment for lower-risk myelodysplastic syndrome (LR-MDS), with particular consideration of ribosomal stress (RS) status and serum erythropoietin (EPO) levels, emphasizing its potential to improve hemoglobin levels and transfusion independence in this patient population.

Panelists discuss key takeaways from the COMMANDS trial, including the analysis of biomarkers in responders by ribosomal stress status (Hayati et al, EHA 2024), the impact of luspatercept on cell lineages (Garcia-Manero et al, EHA 2024), and the long-term clinical value of extended RBC transfusion independence (RBC-TI) (Garcia-Manero et al, ASH 2024).

Panelists discuss how mutational burden impacts the response to frontline luspatercept in lower-risk myelodysplastic syndrome (LR-MDS), highlighting its role in predicting treatment outcomes and the duration of transfusion independence.

Panelists discuss how mutational burden influences the duration of response to frontline luspatercept in lower-risk myelodysplastic syndrome (LR-MDS), as observed in the COMMANDS trial (Komrokji et al, EHA 2024), and when luspatercept should be chosen as a first-line treatment, considering its use before or alongside transfusion; they also explore the impact of luspatercept on hemoglobin levels and quality of life (Oliva et al, EHA 2024; Santini et al, ASH 2024), and the key factors in selecting between available treatment options for initial anemia management.

Panelists discuss dosing strategies for frontline luspatercept in lower-risk myelodysplastic syndrome, emphasizing individualized approaches to optimize efficacy and minimize adverse effects based on patient response and clinical factors.

Panelists discuss real-world evidence on dose escalation of luspatercept in lower-risk myelodysplastic syndrome (LR-MDS) (Patel et al, EHA 2024), highlighting its clinical benefits in improving patient outcomes, and share insights from the MAXILUS trial (Della Porta et al, EHA 2024), considering how this dosing strategy could influence clinical practice and enhance patient care.

Panelists discuss second-line (2L) treatment strategies for lower-risk myelodysplastic syndrome (LR-MDS), focusing on how to choose a 2L treatment for patients refractory to first-line options, and provide an overview of recent updates from the IMerge trial (Santini et al, EHA 2024; Zeidan et al, JCO 2024), while considering the role of imetelstat in treatment sequencing according to NCCN Guidelines MDS-5.

Panelists discuss key learnings from recent studies on lower-risk myelodysplastic syndrome (LR-MDS) treatment, identify remaining knowledge gaps, and offer final takeaways, including their thoughts on the role of luspatercept in the evolving LR-MDS treatment landscape, clinical pearls for community oncologists, and major unanswered questions that could improve outcomes for LR-MDS and anemia management in the future.