Sotatercept alleviated anemia burden in low-risk myelodysplastic syndrome

Issue: January 25, 2015

SAN FRANCISCO — Treatment with sotatercept was associated with erythroid hematologic improvement and a reduction in red blood cell transfusion burden in anemic patients with lower-risk myelodysplastic syndrome, according to study results.

Perspective from Alan Lichtin, MD

“Anemia is a common complication of myelodysplastic syndrome, one of the most common blood cancers in elderly patients,” Rami S. Komrokji, MD, of the department of malignant hematology at the H. Lee Moffitt Cancer Center and Research Institute, said during a press briefing. “Around 90% of the patients are anemic, and 60% to 70% will become transfusion dependent. Treatment of anemia, especially in lower-risk myelodysplastic syndrome, remains an unmet medical need and challenge. There are currently limited options available or approved for treatment.”

Rami S. Komrokji

Komrokji and colleagues sought to determine a safely tolerated dose of sotatercept (ACE-011; Acceleron, Celgene) for erythroid hematological improvement in patients with myelodysplastic syndrome-associated anemia.

The analysis included 54 patients with International Prognostic Scoring System-defined low- or intermediate-1 risk for myelodysplastic syndrome or nonproliferative chronic myelomonocytic leukemia (median age, 71 years). Patients’ median time from diagnosis was 4 years (range, 0-31), and 70% of the patients were male.

All patients had anemia with hemoglobin levels ≤9 g/dL and 94% of patients had not responded with or had lost their response to erythropoiesis-stimulating agents.

Patients received a median of six (range, 0-18) red blood cell unit transfusions in the 8 weeks before study enrollment. Forty-five patients had a high transfusion burden, defined by the receipt of four or more transfusions in the 8 previous weeks.

Researchers assigned patients 0.1-mg/kg (n=7), 0.3-mg/kg (n=6), 0.5-mg/kg (n=21) or 1-mg/kg (n=20) doses of sotatercept subcutaneously once every 3 weeks.

Efficacy data were available from 53 patients. Of them, 24 (45%) achieved erythroid hematological improvement.

Nineteen of 44 patients who had a high transfusion burden responded with a reduction of four or more transfusions during 8 weeks. Five patients achieved transfusion independence, and the duration of transfusion independence ranged from 62 to 345 or more days.

Five of nine patients with a low transfusion burden experienced hemoglobin increases ≥1.5 g/dL for 8 or more weeks and achieved transfusion independence. Sixty-seven percent of these patients received the 1-mg/kg dose, and 33% received the 0.5-mg/kg dose.

Researchers noted patients with baseline thrombocytopenia demonstrated platelet increases, and patients with baseline neutropenia experienced increased neutrophil levels.

Twenty patients experienced at least one adverse event, the most common of which were fatigue (11%), headache (9.3%), decreased appetite and nausea (both 7.4%).

Thirty-five patients discontinued sotatercept treatment, 28 of whom discontinued due to a lack of treatment effect. One patient each discontinued due to treatment-related grade 2 hemolytic anemia, grade 3 hypertension and grade 2 muscular weakness.

“Sotatercept showed promising evidence of clinical activity in this cohort of lower-risk myelodysplastic syndrome patients who were anemic and refractory to erythropoiesis-stimulating agents with a challenging and unmet need for treatment,” Komrokji said. “Further exploration of higher sotatercept doses and longer-term treatment is planned and ongoing.”

For more information:

Komrokji RS. Abstract #3251. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.

Disclosure: Komrokji reports a consulting relationship with Celgene. Other researchers report consultant/advisory, employment and board of director roles with; research funding from; and equity ownership in Acceleron Pharma, Amgen, Boehringer-Ingelheim, Celgene, Novartis and US Oncology.

Perspective

Alan Lichtin, MD

There is so much interplay of the different regulators in erythropoiesis that this study might shed some light on this area. Any improvements in hemoglobin that we see in this patient population, whether they have thalassemia or myelodysplastic syndrome, is wonderful. But, it’s too early to say whether this study is going to be a home run.
The complexity of how erythropoiesis occurs has to be weighed into the decision-making on how to treat one patient vs. another. For example, if you have a patient with chronic myelomonocytic leukemia or myelodysplasia, they may have some other mutation in some other regulatory pathway and, thus, they may or may not respond how you would expect them to. If you tug at one end of the black box, there could be effects at the other end of the black box. Improvement in hemoglobin or a reduction in transfusion may be wonderful endpoints, but you don’t know whether the agent you gave acted the way you expected because of the possibility of interplay between other regulators.

Alan Lichtin, MD

Cleveland Clinic

Disclosures: Lichtin reports no relevant financial disclosures.