Luspatercept Improves Anemia Metrics Across Myelofibrosis Cohorts

In the ACE-536-MF-001 trial, treatment with luspatercept improved transfusion burden and anemia across four cohorts of patients with myelofibrosis and varying transfusion dependency, anemia status, and ruxolitinib exposure, according to a report in Blood Advances.

Additionally, “in most patients, ruxolitinib dose and spleen size remained stable,” wrote the study’s lead author, Aaron Gerds, MD, MS, of Cleveland Clinic Taussig Cancer Institute. The safety profile of luspatercept was also “consistent [with] previous studies.”

Luspatercept for Anemia Treatment

The ACE-536-MF-001 trial enrolled 95 patients with myelofibrosis into the following four cohorts:

• Cohort 1: transfusion-independent with anemia
• Cohort 2: transfusion-dependent
• Cohort 3a: transfusion-independent with anemia with stable ruxolitinib prior to and during study
• Cohort 3b: transfusion-dependent with stable ruxolitinib prior to and during study

All study participants received luspatercept at doses of 1.0 mg/kg to 1.75 mg/kg in 21-day cycles. Luspatercept was continued if patients showed a clinical benefit on day 169.

The primary endpoint was anemia response rate over any 12-week period from week one to week 24, with response defined as hemoglobin increase of 1.5 g/dL or greater in nontransfusion-dependent patients and transfusion independence in transfusion-dependent patients.

In total, 14%, 10%, 14%, and 26% of patients in cohorts 1, 2, 3a, and 3b achieved the primary end point, respectively. Additionally, 27% of patients in cohort 1 and 50% in cohort 3a had mean hemoglobin increases of 1.5 g/dL or more from baseline, and around 50% of transfusion-dependent patients in cohorts 2 and 3b had 50% or greater reductions in transfusion burden.

Total symptom score was reduced in all cohorts, with the greatest rate of response observed in cohort 3a, according to the authors.

One or more adverse events (AEs) occurred in 94% of patients and 47% of patients had one or more treatment-related AE (grade 3 or higher, 11%), most commonly hypertension (18%). One patient discontinued luspatercept due to a serious treatment-related AE. Nine patients died during treatment unrelated to luspatercept.

Reference

Gerds AT, Harrison CN, Kiladjian JJ, et al. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. https://doi.org/10.1182/bloodadvances.2024012939