Improving Luspatercept Titration and Persistence in Community Practice

Amer Zeidan, MBBS, MD, and Raji Shameem, MD, discussed real-world underdosing of luspatercept-aamt (Reblozyl) in lower-risk myelodysplastic syndromes (MDS).

Real-world analyses suggest that a substantial share of patients who discontinue treatment do so before reaching the maximum 1.75 mg/kg dose, often after being deemed nonresponders at the 1 mg/kg starting dose.¹ Both physicians stressed that education and reinforcement around appropriate titration are essential, as most patients with lower-risk MDS will need long-term therapy. They also noted that full-dose initiation could help some patients avoid premature discontinuation.

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: Real-world data show that over 36% of patients discontinue luspatercept before ever reaching the top dose. What needs to happen to better educate community oncologists on proper titration and staying the course?

Shameem: I can tell you that where I practice in Florida, this was a real issue, and we’re doing better. You’d be surprised how many patients started at 1 mg/kg with no dose escalation, and the treatment was then deemed ineffective. For lower-risk MDS, I want my patients to see every therapy, and I try to achieve the maximum benefit possible because it’s a marathon for them. It has changed over time. I see more dose escalations now, appropriately titrating based on hemoglobin, but we can always do better. In the trial, most patients required dose escalation and a large number ended up around the highest dose. I see a positive change, but we could get the word out even better for our patients.

Zeidan: I agree. Education and reinforcement are vital because it’s unfortunate if a patient is discontinued from luspatercept before reaching the full dose. Most patients with lower-risk MDS will have MDS for the rest of their lives. Most will not go to transplant and will need to be on some kind of treatment, so prematurely discontinuing any drug is not a good idea because it limits subsequent options. Hopefully, with more dissemination, education, and reinforcement, most people will remember this. As we discussed, the MAXILUS [NCT06045689] approach of starting at the top dose from the outset could be another solution to avoid this issue for some patients.

References

1. Sekeres MA, Hnoosh A, Yucel A, et al. Real-world treatment patterns and outcomes of first-line luspatercept in patients with myelodysplastic syndromes in the United States. Blood. 2025;146(suppl 1):5638. doi:10.1182/blood-2025-5638
2. Della Porta MG, Diez-Campelo M, Santini V, et al. Luspatercept initiated at the maximum-approved dose in patients with lower-risk myelodysplastic syndromes who require transfusions: primary analysis from MAXILUS. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S173.