Luspatercept Is Effective Treatment for Anemia Post-Allo-HSCT in Patients With Hematologic Conditions

According to newly published research in Blood Cancer, luspatercept (Reblozyl; Bristol Myers Squibb) was effective as a therapeutic option for patients with anemia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat their hematologic condition. These results could serve as guidance for clinicians and providers when treating patients with anemia, which is a common complication of allo-HSCT.¹

Luspatercept, a specific activin receptor fusion protein that reduces SMAD2 and SMAD3 signaling through the binding of superfamily ligands, has been proven effective as a red blood cell maturation agent by the FDA. Studies have indicated its effectiveness in reducing red blood cell infusion burden in adults with low-to-moderate-risk myelodysplastic syndrome (MDS) with ring sideroblasts (RS) or SF3B1 mutation. Additionally, a trial found that the therapy improved anemia in patients with myelofibrosis by increasing hemoglobin levels and reducing transfusion burden.^1-3

Anemia is a common complication of allogeneic stem cell transplantation. | Image Credit: © Ployker - stock.adobe.com

Given the common occurrence of anemia in these patients and the concerning complications of immunosuppressive treatments typically used for hematological conditions, the current investigators sought to further examine the efficacy and safety of luspatercept. In this study, they retrospectively analyzed 16 patients with anemia following allo-HSCT to better elucidate their outcomes and potential improvements in their condition.¹

The baseline characteristics of the patients in the analysis were listed. Across the cohort, underlying diseases included acute myelocytic leukemia (n = 6), severe aplastic anemia (n = 4), acute lymphoblastic leukemia (n = 3), myelodysplastic syndrome (n = 2), and T lymphoblastic leukemia (n = 1). Prior to receiving allo-HSCT, patient disease status across the cohort was complete response (37.5%), partial response (43.8%), and non-response (18.7%). Luspatercept therapy was initiated a median of 134.5 days following allo-HSCT.¹

Among the enrolled patients, 13 (81.3%) achieved erythroid response following luspatercept treatment, and throughout these responders, 4 (30.8%) remained transfusion-independent until the last follow-up visit. In comparing mean neutrophil counts, the investigators observed an increase (2.2 (0.39–4.76) × 10⁹/L vs 1.7 (0.35–6.1) × 10⁹/L) following luspatercept treatment compared with prior.¹

Regarding safety, patients had an overall tolerable profile of adverse events. Throughout treatment, 1 patient reported experiencing fatigue, 1 patient reported palpitations, and another reported limb edema. According to the investigators, those symptoms were consistent with grade 1 toxicity and resolved spontaneously within 1 week of their appearance. In a promising development, no patients developed obvious grade 2 through 4 toxicities, including diarrhea, nausea, dizziness, or back pain. Furthermore, the overall survival rate for all patients was 93.8%, a strong sign of anemia improvements.¹

Other clinical trials have evaluated luspatercept’s efficacy in a variety of patient populations. In the MEDALIST clinical trial, luspatercept induced a hematologic improvement-erythroid rate of 53% and a red blood cell transfusion independence rate of 38% in patients with MDS-RS during the first 24 weeks of treatment. In another trial, BELIEVE, luspatercept enabled 11% of patients to achieve transfusion independence during any 8-week interval. Therefore, the results from the current trial compare favorably to prior literature and demonstrate that luspatercept is an efficacious option for treating anemia.^1,4,5

REFERENCES

1. Xin X, Zhang W, Li Z, et al. Luspatercept for the treatment of anemia in allo-HSCT for patients with hematological diseases. Blood Cancer J. 2025;15(12). doi:10.1038/s41408-025-01218-8

2. Platzbecker U, Germing U, Götze KS, et al. Luspatercept for the treatment of anemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. The Lancet Oncology. 2017;18(10):1338-1347. doi:10.1016/S1470-2045(17)30615-0

3. Gerlach A. Study demonstrates safety, efficacy of luspatercept for MF-related anemia. Pharmacy Times. Published September 19, 2024. Accessed March 5, 2025. https://www.pharmacytimes.com/view/study-demonstrates-safety-efficacy-of-luspatercept-for-mf-related-anemia

4. Fenaux P, Platzbecker U, Mufti GJ, et al. The Medalist trial: Results of a phase 3 randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions. Blood. 2018;132(1). doi:10.1182/blood-2018-99-110805

5. Cappellini MD, Viprakasit V, Phil D, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. New Engl J Med. 2020;382(13):1219-1231. doi:10.1056/NEJMoa1910182