Sequencing Therapy After ESA Failure in RS-Negative Lower-Risk MDS

After a Frontline Forum program, Amer Zeidan, MBBS, MD, and Raji Shameem, MD, discussed how they sequence therapy for patients with ring sideroblast (RS)–negative lower-risk myelodysplastic syndromes (MDS) after failure of an erythropoiesis-stimulating agent (ESA).

Zeidan outlined a sequence beginning with luspatercept-aamt (Reblozyl) followed by imetelstat (Rytelo) and then potentially a hypomethylating agent (HMA) or a trial of lenalidomide (Revlimid), with close monitoring for clonal evolution and early consideration of transplant in patients who are eligible. Shameem described a similar approach, favoring luspatercept first regardless of RS status.

Zeidan is a professor of medicine at Yale School of Medicine and chief of the Division of Hematologic Malignancies, director of Hematology Early Therapeutics Research, and assistant director of the Clinical Trial Office for Hematology at Yale Comprehensive Cancer Center. Shameem is a hematologist and medical oncologist at the Orlando Health Cancer Institute.

Transcript:

CancerNetwork: Patients with RS-negative lower-risk MDS typically face narrower timelines. Per the latest data and guidelines, what is your go-to sequencing logic once an ESA fails them?

Zeidan: Patients who are RS positive have a more indolent natural history and generally better survival, whereas some patients with lower-risk RS-negative disease may be higher risk by molecular IPSS from the outset, as we mentioned, so it’s important to identify those patients. For a patient whose predominant problem is anemia without other high-risk features after an ESA, if they have not received luspatercept, I would give luspatercept at that point, then imetelstat. After that, potentially a HMA or a trial of lenalidomide. I would monitor the patient very closely during their journey for evidence of clonal evolution or high-risk features, such as an increase in the blast count or cytogenetic alterations. At any point, if the patient is a transplant candidate, I would consider transplant, especially after failure of at least luspatercept and imetelstat. Once I start giving an HMA, I begin thinking very seriously about transplant.

Shameem: I agree. I have a similar treatment flow in my practice, where I would use luspatercept and consider imetelstat afterward. For those patients, [I would consider] hypomethylating agents as well. But I tend to use luspatercept first for patients in the frontline setting regardless of RS-positive or RS-negative status.