Luspatercept in the treatment of patients with lower-risk myelodysplastic neoplasms

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Abstract

Background. Anemia and transfusion dependence (TD) impair quality of life and survival in patients with lower-risk myelodysplastic neoplasms (MDS). Luspatercept, an activin receptor ligand inhibitor, represents a new class of drugs for correcting anemia in MDS.

Aim. To evaluate the efficacy and safety of luspatercept in patients with lower-risk MDS and TD based on clinical trial data and real-world clinical practice.

Materials and methods. A search from 2011 to 2025 for the key clinical trials (MEDALIST, COMMANDS) and recent publications was performed, and experience with luspatercept in clinical practice is presented.

Results. In the MEDALIST trial, among patients with ring sideroblasts refractory to erythropoiesis-stimulating agents, luspatercept provided transfusion independence ≥ 8 weeks in 38 % of patients (vs. 13 % in the placebo group). In the COMMANDS trial luspatercept was superior to epoetin α in achieving transfusion independence ≥ 12 weeks (59 % vs. 31 %). The highest efficacy was observed in patients with the SF3B1 mutation, low transfusion burden (< 4 RBC units / 8 weeks), and an endogenous erythropoietin level > 80 IU / L. Real-world data confirm these results.

Conclusion. Luspatercept has become the new standard of care for anemia in transfusion-dependent patients with lower-risk MDS, demonstrating high efficacy both after erythropoiesis-stimulating agent failure and as first-line therapy, especially in the subgroup with ring sideroblasts and the SF3B1 mutation.

About the authors

K. S. Tsvirko

Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I. P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: Ksenia_Kud_@mail.ru
ORCID iD: 0000-0002-9032-6885
Russian Federation, 6–8 L'va Tolstogo St., Saint Petersburg, 197022

N. Y. Tsvetkov

Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I. P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia

Email: Ksenia_Kud_@mail.ru
ORCID iD: 0000-0002-8401-0817
Russian Federation, 6–8 L'va Tolstogo St., Saint Petersburg, 197022

E. V. Morozova

Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation, I. P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia

Email: Ksenia_Kud_@mail.ru
ORCID iD: 0000-0003-0752-0757
Russian Federation, 6–8 L'va Tolstogo St., Saint Petersburg, 197022

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