15 HLA-MATCHED ALLOGENEIC STEM CELL TRANSPLANTATION IMPROVES OVERALL SURVIVAL OF HIGHER RISK MYELODYSPLASTIC SYNDROME

Abstract

sotatercept (ACE-011), a novel first-in-class activin type IIA receptor fusion protein, in anemic patients with IPSS Low/Intermediate-1risk MDS or non-proliferative CMML. ClinicalTrials.gov identifier: NCT01736683. Methods: The primary endpoint of this study is erythroid hematological improvement (HI-E; defined by modified IWG 2006 criteria). Secondary endpoints include rate of RBC-transfusion independence (RBC-TI) ≥8 weeks and safety. Eligible patients have lower-risk MDS or non-proliferative CMML and anemia, with no response, loss of response, or low chance of response to ESAs. Patients receive subcutaneous sotatercept at 0.1, 0.3, 0.5, or 1.0 mg/kg every 3 weeks. Results: As of May 22, 2014, 54 MDS patients were enrolled: 7, 6, 21, and 20 in the sotatercept 0.1, 0.3, 0.5, and 1.0 mg/kg groups, respectively. Median age 71 years, median time from diagnosis 4 years, and 70% of patients were male. Patients received a median 6 RBC units (range 0–16) in the 8 weeks before starting treatment; 46 received ≥4 RBC units (high transfusion burden; HTB) and 8 received. Of 53 patients evaluable for efficacy, 24 achieved HI-E: 0, 4, 8, and 12 patients in the sotatercept 0.1, 0.3, 0.5, and 1.0 mg/kg groups, respectively. Five of 46 (11%) HTB patients achieved RBCTI ≥8 weeks; duration of response ranged from 59–345+ days. Five of 8 (63%) LTB patients achieved RBC-TI ≥8 weeks with a mean hemoglobin increase of ≥1.5 g/dL sustained for ≥8 weeks; duration ranged from 76–233+ days. Sotatercept was generally well tolerated. Twenty (37%) patients reported ≥1 suspected treatment-related adverse event. The most common were: fatigue/asthenia (13%), headache (9%), decreased appetite (7%), and nausea (7%). Three patients discontinued due to suspected treatment-related adverse events: 1 each with grade 2 hemolytic anemia, grade 3 hypertension, and grade 2 muscular weakness in the sotatercept 0.3, 0.5, and 1.0 mg/kg groups, respectively. Conclusions: Sotatercept was well tolerated, with promising evidence of clinical activity in this cohort of anemic, lower-risk MDS patients. Further exploration of sotatercept treatment is ongoing. PF and AFL contributed equally to this abstract as senior coauthors.