Luspatercept has ‘Limited Therapeutic Value’ in Anemia, Myelofibrosis

Findings from a new study “underscore the limited therapeutic value of luspatercept” in patients with anemia and myelofibrosis.

The study included 37 consecutive patients with myelofibrosis or myeloid neoplasms other than myelodysplastic syndrome (MDS) with ring sideroblasts who received treatment with luspatercept outside the clinical trial setting between July 2020 and May 2022. Of the 37 patients, 10 had myelofibrosis-related anemia, while 27 patients had MDS, a myeloproliferative neoplasm, or chronic myelomonocytic leukemia.

Of the 37 patients, three met the criteria for anemia response to treatment, including two of the 24 patients who were transfusion dependent and one who was transfusion independent. The median time to anemia response was six months. None of the patients with thrombocytopenia had improvement in platelet counts.

“A noteworthy observation included the timing of luspatercept which was initiated later in the disease course in responders at a median of 57 months from MDS diagnosis compared to 14 months in non-responders, suggesting indolent disease biology,” the study’s authors wrote.

Most patients (81%) discontinued treatment, with the most common reason being a lack of response. The most frequently reported treatment-related adverse events included fatigue, lightheadedness, abdominal pain, muscle aches, bone aches, dyspnea, hypertension, headaches, chest tightness, and palpitations.

“The findings from the current study underscore the limited therapeutic value of luspatercept in anemic patients with [myelofibrosis] as none of the 10 patients including those on concomitant ruxolitinib fulfilled criteria for erythroid response,” the study’s authors concluded. “In contrast, in patients [with myelofibrosis who were] treated with the JAK2 inhibitor momelotinib in the clinical trial setting, transfusion independence was achieved in 19 of 37 (51%) transfusion-dependent patients …. Our observations highlight the need for careful risk benefit assessment prior to luspatercept use and an alternative management approach to [myelofibrosis] and low-risk MDS related anemia is advised.”

Reference

Gangat N, Chetram D, McCullough K, et al. Limited activity of luspatercept in myelofibrosis and myeloid neoplasms other than myelodysplastic syndromes with ring sideroblasts. Am J Hematol. 2022;97(12):E474-E477. doi:10.1002/ajh.26749