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June 13, 2023/Cancer/Research

Luspatercept Shows Promise as Treatment for Anemia in Patients With Myelofibrosis

Approach resulted in transfusion independence and durable anemia response

23-CNR-3898263-CQD-Hero-650×450 Gerds

Treatment with luspatercept led to promising improvements in anemia and transfusion dependence among patients with myelofibrosis. This research, which was recently presented during the American Society of Clinical Oncology annual meeting, also showed a safety profile consistent with previously reported data.


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“Anemia is incredibly common in patients with myelofibrosis,” notes study author Aaron T. Gerds, MD, Associate Professor of Medicine of Hematology & Medical Oncology, and Deputy Director for Clinical Research for Cleveland Clinic. “It is estimated that 40% of patients will have anemia at the time of diagnosis, and many will develop chronic anemia.

“This is a significant burden on both patients and the medical system,” he says. “If we can find ways to reduce anemia and eliminate transfusion burden among this patient population, it will not only help individuals, but our medical system in its entirety.

Study specifics

The phase 2, multicenter, open-label ACE-536-MF-001 study examined the efficacy and safety of luspatercept in patients with myeloproliferative neoplasm-associated myelofibrosis and anemia with and without red blood cell transfusion dependence.

Eligible patients were enrolled and treated in four cohorts based on transfusion dependence and stable ruxolitinib treatment, according to the study authors. The cohorts were as follows:

  • Cohort 1: non-transfusion dependent, no ruxolitinib
  • Cohort 2: transfusion dependent, no ruxolitinib
  • Cohort 3A: non-transfusion dependent, ruxolitinib
  • Cohort 3B: transfusion dependent, ruxolitinib

The primary endpoint was anemia response. Secondary endpoints included duration of response, transfusion frequency, change in hemoglobin level and symptom response. Patients were administered subcutaneous luspatercept 1.0 mg/kg (1.33 mg/kg for patients in cohort 3B expansion) with titration up to 1.75 mg/kg in 21-day cycles.

Key takeaways

Of the 95 patients in the intention-to-treat population, a lack of clinical benefit at day 169 (n = 28) was the most common reason for treatment discontinuation. Loss of response (13.7%), lack of efficacy after day 169 (12.6%) and withdrawal by the patient (12.6%) were other reasons for discontinuation.

The median age of included patients was 71 years. The majority of study participants had primary myelofibrosis (54.7%), intermediate-2 risk score (75.8%) and more than two years since initial diagnosis (74.7%).

“Treatment with luspatercept led to transfusion independence in transfusion-dependent patients and durable anemia response in non-transfusion dependent patients,” says Dr. Gerds, while noting that these findings demonstrated clinical benefit among patients in all four cohorts.


Data also showed that approximately half of transfusion-dependent patients who underwent treatment with luspatercept achieved a 50% reduction in transfusion burden.

Patients receiving ruxolitinib in combination with luspatercept—cohort 3—had the greatest anemia response in the entire treatment period, the study authors reported (31.6%, cohort 3B; 21.4%, cohort 3A). The anemia response rate in the primary treatment period among non-transfusion dependent patients was 13.6% in cohort 1 and 14.3% in cohort 3A. The median time to achieve anemia response in cohorts 1 and 3A was 63 days and 63.5 days, respectively.

The transfusion independence rate in the primary treatment period for transfusion-dependent patients was 9.5% in cohort 2 and 26.3% in cohort 3B. Median time to transfusion independence in cohorts 2 and 3B was two days and 27 days, respectively.

Data showed that the safety profile of luspatercept was consistent with previous research, and no new safety signals were identified. The most common treatment-related adverse event was hypertension. However, Dr. Gerds and colleagues reported that cases were generally low-grade and manageable. None of these cases led to discontinuation of luspatercept.

Additionally, the study authors observed low transformation rates to acute myeloid leukemia (2 patients, 2.2%), which were unrelated to study treatment. Overall, no deaths were associated with luspatercept treatment.

Clinical significance

These findings demonstrated that luspatercept improved anemia in a large number of patients, with limited toxicity, according to Dr. Gerds, who notes that this opens the door for further investigation.

“If anemia is multifactorial—meaning there are multiple causes for anemia in any given individual—we can attack it from multiple different directions with combination therapy,” he says. “Since luspatercept was safely combined with ruxolitinib, we could potentially combine it with other agents that may improve anemia.

“Not only are we improving patients currently with single-agent luspatercept, but the prospect in the future of combination therapies is very exciting,” concludes Dr. Gerds. “These findings highlight the need for further study, and the phase 3 INDEPENDENCE study (ACE-536-MF-002) is currently underway.”


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