A novel agent holds promise as a treatment option for anemia in patients with lower-risk myelodysplastic syndromes who are not helped by erythropoiesis-stimulating agents (ESAs), according to results from a phase 2 trial.

Sotatercept (ACE-011) is a first-in-class novel recombinant fusion protein, and was found to be effective and well tolerated, increasing hemoglobin concentrations and decreasing the transfusion burden in this patient population.

Nearly half (29, 47%) of 62 patients with a high transfusion burden achieved hematologic improvement–erythroid (HI-E), which for them was a reduction in red blood cell transfusion from baseline of 4 U or more for at least 56 days. Additionally, 7 of 12 patients (58%) with a low transfusion burden also achieved HI-E, defined as an increase in hemoglobin of 1.5 g/dL or more that was sustained for at least 56 days without a transfusion.

“Taken together, these findings provide proof of principle that the recombinant protein sotatercept can restore ineffective erythropoiesis in patients with lower-risk myelodysplastic syndromes, with an acceptable safety profile,” Rami Komrokji, MD , of Moffitt Cancer Center and Research Institute, Tampa, and his colleagues, wrote in the Lancet Haematology .

There are few effective treatment options available for patients with lower-risk myelodysplastic syndromes who have anemia, especially after they fail primary or secondary treatment with ESAs, or for those who are not likely to benefit from ESA therapy.

In this phase 2 trial, the researchers sought to establish a safe and effective dose of sotatercept in a cohort of 74 patients. Of this group, 7 received 0.1 mg/kg sotatercept, 6 got 0.3 mg/kg, 21 received 0.5 mg/kg, 35 got 1.0 mg/kg, and 5 patients received doses up to 2.0 mg/kg. The primary efficacy endpoint of the study was the proportion of patients who achieved HI-E.

All of the patients were pretreated, having received prior therapy for myelodysplastic syndromes, including ESAs, hypomethylating agents (azacitidine or decitabine), lenalidomide, and other agents including corticosteroids and immunomodulators.

Within this cohort, 36 patients (49%; 95% confidence intervaI, 38-60) achieved HI-E while 20 patients (27%; 95% CI, 18-38) achieved independence from transfusion for at least 56 days.

Fatigue (26%) and peripheral edema (24%) were the most common adverse events reported, while grade 3-4 treatment-emergent adverse events (TEAEs) were reported in 34% of patients. Of these, 4 patients had grade 3-4 TEAEs that were probably related to the treatment. The most common grade 3-4 TEAEs were lipase increase and anemia, and each was reported in three patients. Additionally, 17 patients (23%) experienced at least one serious TEAE, including a death from a treatment-emergent subdural hematoma (which caused the patient to fall).

The study was funded by the Celgene. Dr. Komrokji reported financial relationships with Celgene and Novartis. Other study authors reported relationships with various pharmaceutical companies.

SOURCE: Komrokji R et al. Lancet Haematol. 2018 Jan 10. doi: 10.1016/S2352-3026(18)30002-4 .