Researchers from the 2021 American Society of Hematology (ASH) Annual Meeting found sotatercept to be safe and effective for anemic patients with myeloproliferative neoplasm (MPN)-associated myelofibrosis (MF).

A response rate of 30% was shown when used alone, but increased to 32% when combined with a stable dose of ruxolitinib.

“Anemia is an on-target effect of therapeutic Janus kinase 2 (JAK2) inhibition, and is a frequent cause of ruxolitinib discontinuation in clinical practice,” the study authors explained. “Current therapies for anemia of MF (erythropoietin and analogs, danazol, IMiDs) are unsatisfactory. Sotatercept is a first-in-class, activin receptor type IIA ligand trap that may improve anemia by sequestering stromal transforming growth factor beta superfamily ligands that suppress terminal erythropoiesis.”

The phase 2, investigator-initiated, open-label, single institution study administered sotatercept subcutaneously, every 3 weeks among 2 groups of anemic patients with MPN-associated MF (Hemoglobin <10 g/dl on every determination for 12 weeks, or transfusion-dependent (TD) per IWG-MRT criteria with MF.)

Treatment was given as a single agent and in combination with a stable dose of ruxolitinib. In order to be considered “response-evaluable,” patients had to be on-study for more than 12 weeks (84 days). Patients on ruxolitinib must have been on it for ≥6 months with a stable dose for the next ≥8 weeks, and received a sotatercept dosage of 0.75 mg/kg. Monotherapy patients received a dosage of sotatercept that was either 0.75 or 1 mg/kg. Both groups defined an anemic response as transfusion-dependent patients achieving transfusion independence, or an increase in hemoglobin level from baseline of ≥1.5 g/dl sustained for ≥12 weeks in non-TD patients.

Of 56 patients treated, 34 received sotatercept alone while 21 received a combination with ruxolitinib. Further, 17 TD and 17 non-TD patients received sotatercept alone for a median of 11 cycles, 16 patients received 0.75 mg/kg, and 18 patients received 1 mg/kg. The researchers recorded 6 responses at the 0.75 mg/kg dose, and 2 at the 1 mg/kg dose. The median time to response was “19 (1-22) days and median duration of response (DOR), 23.3 (3.9-68.4) months.”

Among the cohort receiving combination therapy, there were 15 non-TD patients and 6 TD patients. The median dose of ruxolitinib at study entry was 10 (5-25) mg, and the median number of cycles was 25. Of the 19 evaluable patients in the combination cohort, 6 responded and were all non-TD patients. The time to response was 14 (6-147) days.

The researchers explained that they observed several “non–response-evaluable patients in both cohorts.”

Overall, sotatercept was “well-tolerated”, the researchers said, with some adverse events (AEs), including hypertension (n=7) and limb (bone/muscle/joint) or back pain (n=2).

“Sotatercept is safe and effective against anemia of MPN-associated MF, both in non-TD and TD pts, with a response rate of 30% when used alone and 32% when used in conjunction with a stable dose of ruxolitinib,” researchers concluded. “All responses in the ruxolitinib cohort occurred in non-TD patients.”—Cristalia Turck

Bose P, Masarova L, Pemmaraju N. Final Results of a Phase 2 Study of Sotatercept (ACE-011) for Anemia of MPN-Associated Myelofibrosis. Presented at: The 2021 ASH Annual Meeting; December 11-14, 2021; Abstract 144.