Study Demonstrates Safety, Efficacy of Luspatercept for MF-Related Anemia

Luspatercept (Reblozyl; Bristol Myers Squibb) improved anemia in patients with myelofibrosis (MF) with or without transfusion dependence, according to findings published in Blood Advances. By effectively increasing hemoglobin levels and reducing transfusion burden, luspatercept offers a new therapeutic option that addresses a critical aspect of patient care in this challenging condition.¹

Considering the limitations of current treatments and the associated AEs, luspatercept represents an advancement in the management of MF-related anemia. Image Credit: © Sittipol - stock.adobe.com

MF is a fatal myeloproliferative neoplasm (MPN) characterized by the uncontrolled proliferation of clonal hematopoietic stem cells, leading to significant scarring in the bone marrow and progressively impaired red blood cell (RBC) production. Approximately 40% of patients with MF have anemia at diagnosis, of which an estimated 25% are RBC transfusion dependent (TD). Many patients will develop chronic anemia and become increasingly TD as the disease progresses, worsening their overall survival outcomes.^1,2

Janus kinase inhibitors (JAKis), such as ruxolitinib (Jakafi; Incyte Corp), are recommended treatment options for patients with MF that provide durable symptom relief and are generally well-tolerated. However, patients not previously treated with JAKis can develop grade 3 or 4 anemia during these treatments, and the standard-of-care treatments for MF-related anemia are often associated with multiple adverse effects (AEs).¹

Luspatercept is an erythroid maturation agent that binds to proteins within the tumor growth factor β superfamily to reduce interfere with Smad2 and Smad3 signaling pathways, which promotes red blood cell production. According to data from the phase 2, multicenter, open-label ACE-536-MF-001 trial (NCT03194542), luspatercept demonstrated favorable increases in hemoglobin levels and reductions in transfusion burden in patients with MF.^1,3

The trial enrolled 95 patients who were divided into 4 cohorts: patients in cohorts 1 and 3A were non–transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All the participants received 1.0 to 1.75 mg/kg of luspatercept for 21-day cycles with a treatment extension upon observed clinical benefit at day 169. The primary end point of the study 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. Secondary end points included ≥50% reduction in total symptom score or ≥50% reduction in fatigue symptom.¹

Luspatercept achieved its primary end point in 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B, and particularly for those receiving ruxolitinib. The study authors observed a mean hemoglobin increase of ≥1.5 g/dL from baseline in patients from cohorts 1 (27%) and 3A (50%). In the TD group, approximately 50% of patients had ≥50% reduction in transfusion burden and there was a reduction in total symptom score in all cohorts, with the greatest response in cohort 3A.¹

Of the participants, 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%) that was managed with medical intervention. After 3 years of minimal follow-up, the luspatercept safety profile was consistent with previous studies.¹

The findings from the ACE-536-MF-001 trial underscore the significant potential of luspatercept in improving anemia for patients with MF, whether TD or not. Considering the limitations of current treatments and the associated AEs, luspatercept represents an advancement in the management of MF-related anemia, enhancing the quality of life for patients and helping improve overall health outcomes.

REFERENCES

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

2. Myelofibrosis. Mayo Clinic. December 28, 2022. Accessed September 19, 2024. https://www.mayoclinic.org/diseases-conditions/myelofibrosis/symptoms-causes/syc-20355057#:~:text=Myelofibrosis%20is%20an%20uncommon%20type,can%20cause%20weakness%20and%20fatigue

3. A safety and efficacy study to evaluate luspatercept in subjects with myeloproliferative neoplasm-associated myelofibrosis who have anemia with and without red blood cell-transfusion dependence. ClinicalTrials.gov Identifier: NCT03194542. Updated August 24, 2023. Accessed September 19, 2024. https://clinicaltrials.gov/study/NCT03194542