Dr Zeidan on Classification and Treatment Updates in MDS

Amer Zeidan, MBBS, associate professor, internal medicine (hematology), director, Early Therapeutics Research, Hematology, leader, Clinical Research Team for Leukemias and Myeloid Malignancies, chair, Protocol Review Committee I, assistant medical director, Clinical Trials Office, director, Hematology Research Seminar Series, Hematology, member, Executive Committee, member, Clinical Trials Advisory Committee, interim chief, Hematologic Malignancies, Yale Cancer Center, discusses classification and treatment updates for patients with myelodysplastic syndrome (MDS).

Primary updates concerning the classification of MDS in 2022 and 2023 included the implementation of the 2022 World Health Organization Classification system and the International Consensus Classification system, both of which use genetically informed approaches to categorize patients with MDS, Zeidan says. However, the existence of 2 classification systems can complicate patient categorization and subsequent treatment decision-making in the oncology community. This has prompted several initiatives, including those conducted at Yale Cancer Center, to align these systems, Zeidan notes. Another development in MDS classification is the incorporation of the Molecular International Prognostic Scoring System, which integrates molecular alterations into the risk-stratification process for patients with MDS, Zeidan explains.

Regarding therapeutic advances in lower-risk MDS, the FDA expanded the indication for luspatercept (Reblozyl) to include erythropoiesis stimulating agent (ESA)–naive patients with lower-risk MDS with anemia who may require regular red blood cell (RBC) transfusions, regardless of ring sideroblast status. This protein-transforming growth factor pathway ligan trap was previously approved by the FDA in 2020 for patients with very low– to intermediate-risk MDS with ring sideroblasts who were anemic and transfusion dependent after progression on ESAs. That regulatory decision was supported by findings from the phase 3 MEDALIST trial (NCT02631070).

The phase 3 COMMANDS trial (NCT03682536) provided further therapeutic insights on the use of frontline luspatercept in transfusion-dependent patients with lower-risk MDS, Zeidan emphasizes. In COMMANDS, patients were randomly assigned to receive luspatercept or short-acting ESAs. This trial demonstrated that 58.5% of patients who received luspatercept achieved RBC transfusion independence for at least 12 weeks vs 31.2% of those who received ESAs.