Luspatercept Improves Anemia Among Patients With Myelofibrosis With or Without Transfusion Dependence

According to results from the phase 2, open-label ACE-536-MF-001 trial, luspatercept treatment improved anemia and transfusion burden and demonstrated a consistent safety profile among patients with myelofibrosis (MF)-associated anemia with or without both red blood cell (RBC) transfusion dependence and concurrent Janus kinase (JAK) inhibitor treatment with ruxolitinib.

“There is a need for therapeutic agents that are both highly effective in treating MF-related anemia and have minimal toxic effects. Poor management of anemia necessitates recurrent RBC transfusions that place a major burden on both patients and the health care system,” stated first study author Aaron Gerds, MD, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, and coauthors.

This multicenter study included 95 patients with MF and assigned them to 1 of 4 cohorts based on transfusion dependence and stable ruxolitinib treatment status. Participants were defined as transfusion dependent (TD) (cohorts 2 and 3B) if they received 4 to 12 RBC units during the 12 weeks immediately preceding cycle 1 day 1 (C1D1), or non-transfusion dependent (NTD) (cohorts 1 and 3A) if they had ≥3 hemoglobin (Hb) level measurements of ≤9.5 g/dL recorded on ≥3 different days with no RBC transfusions in the 12 weeks immediately preceding C1D1.

All patients received luspatercept (1 to 1.75 mg/kg in 21-day cycles); treatment was extended if clinical benefit was observed at day 169. The measured primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1 to 24). 

Patients in cohorts 1 and 2 did not receive ruxolitinib, whereas patients in cohorts 3A and 3B received concurrent ruxolitinib. Patients in cohort 3A and the initial cohort 3B were required to have received ≥ 16 weeks of a stable ruxolitinib dose immediately before enrollment. For the cohort 3B expansion, the protocol was amended to require ≥ 40 weeks of prior ruxolitinib treatment without interruptions over 2 consecutive weeks and at least 16 weeks of stable ruxolitinib dose immediately before enrollment.

Results demonstrated that 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had a mean Hb increase of ≥ 1.5 g/dL from baseline. Among patients who were TD, ∼50% had ≥ 50% reduction in transfusion burden. Furthermore, a reduction in total symptom score (TSS) was observed in all cohorts, with the greatest response rate seen in cohort 3A.

According to the reported safety profile, 94% of patients had ≥ 1 adverse event; 47% had ≥ 1 treatment-related adverse events (11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. It was noted that 1 patient had a serious treatment-related adverse event that led to luspatercept discontinuation. Investigators noted that 9 patients died on treatment, which was determined to be unrelated to study drug. In most patients, ruxolitinib dose and spleen size remained stable.

“To conclude, these results emphasize the meaningful anemia improvement in MF-associated anemia in both NTD and TD patients as well as an expected safety profile associated with luspatercept,” concluded Dr Gerds and colleagues.

Overall, “these results support continued study of luspatercept in MF-associated anemia in TD patients receiving concomitant JAKi therapy, which is currently underway in the phase 3 INDEPENDENCE trial (ACE-536-MF-002),” they added.

Source:

Gerds A, Harrison C, Kiladjian J, et al. Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis. Blood Adv. Published online August 28, 2024. doi: 10.1182/bloodadvances.2024012939