Choosing Between Imetelstat and Luspatercept in Second-Line MDS

Following a Frontline Forum program, Amer Zeidan, MBBS, MD, and Raji Shameem, MD, discussed how they choose between imetelstat (Rytelo) and luspatercept-aamt (Reblozyl) for second-line treatment of patients with lower-risk myelodysplastic syndromes (MDS).

They referenced the phase 3 MEDALIST trial (NCT02631070), which evaluated luspatercept in ring sideroblast (RS)–positive disease, and the phase 3 IMerge trial (NCT02598661), which studied imetelstat in patients who were relapsed/refractory to, or ineligible for, erythropoiesis-stimulating agents (ESAs).^1,2 Both physicians favored luspatercept for most patients while reserving imetelstat for select patients with a very high transfusion burden or markedly elevated erythropoietin (EPO) levels.

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: When looking at second-line options like imetelstat vs luspatercept, what are your primary deciders—especially for patients with a high baseline transfusion burden or SF3B1 mutations?

Shameem: For me, I look at multiple features to make a treatment decision. We have data for [patients who are] RS-positive from the relapsed/refractory MEDALIST trial, where luspatercept was evaluated. We also have the telomerase inhibitor imetelstat, which was studied in both [patients who were] RS-positive and RS-negative patients who were ESA relapsed/refractory or ESA ineligible. We look at all these things, [including] SF3B1 status and RS-positive status. Luspatercept has a lot of good data, but I’m not saying every patient should get luspatercept. For certain patients, especially those with a high transfusion burden, I would consider imetelstat as well.

Zeidan: I agree with that approach. For most patients, luspatercept would be my frontline treatment. In the occasional patient with a very high EPO level above 500 mU/mL or an extraordinarily high transfusion burden, I would consider imetelstat as a frontline treatment.

References

1. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382(2):140-151. doi:10.1056/NEJMoa1908892
2. Platzbecker U, Santini V, Fenaux P, et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024;403(10423):249-260. doi:10.1016/S0140-6736(23)01724-5