by Dr. C.H. Weaver M.D. updated 8/2023
The U.S. Food and Drug Administration (FDA) approved Reblozyl® (luspatercept-aamt), the first and only erythroid maturation agent (EMA), for the treatment of anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).1
About MDS
Myelodysplastic syndromes (MDS) are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections.2 People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation. Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections.
About Reblozyl® (luspatercept-aamt)
Reblozyl is an erythroid maturation agent which promotes late-stage red blood cell maturation.
The approval of Reblozyl was based on the findings of MEDALIST clinical trial, which evaluated Reblozyl in RBC transfusion dependent patients with very low-, low- and intermediate-risk non-del(5q) myelodysplastic syndrome with ring sideroblasts who were either refractory or intolerant to prior erythropoiesis-stimulating agent (ESA) therapy or were ESA naïve and unlikely to respond due to endogenous serum erythropoietin ≥200 U/L, and had no prior treatment with disease modifying agents.
A significantly greater proportion of patients achieved independence from RBC transfusions for at least eight weeks and at least 12 weeks of independence from transfusions within the first 24 and 48 weeks of the study. The median survival duration was not significantly improved with Reblozyl in all patients but patients responding to treatment had significantly longer survival than non-responders. The probability of survival at 36-months was 78% compared to 17% for non-responders.2
Low Risk MDA
The FDA has approved Reblozyl for the treatment of anemia without prior erythropoiesis-stimulating agent use in adult patients with very low– to intermediate-risk myelodysplastic syndrome who may require regular red blood cell (RBC) transfusions.4,5
The regulatory decision is supported by interim findings from the phase 3 COMMANDS trial in which Reblozyl had superior efficacy of concurrent RBC transfusion independence and hemoglobin increase when compared with epoetin alfa, irrespective of ring sideroblast status.
The phase 3 COMMANDS trial compared erythropoiesis stimulating agents (ESAs) in patients with ESA-naïve, lower-risk MDS to Reblozyl and demonstrated that 58% of MDS patients who received Reblozyl achieved transfusion independence for at least 12 weeks with hemoglobin increase of at least 1.5 g/dL compared with 31% of patients who received an ESA.3
COMMANDS enrolled 356 patients who had a documented diagnosis of MDS and were considered very low risk, low risk, or intermediate risk with less than 5% blasts in the bone marrow, require RBC transfusion and have an endogenous serum erythropoietin concentration of lower than 500 U/L at the time of screening.4 Patients who were randomly assigned to receive Reblozyl or epoetin alfa and directly compared.
Overall 67% of patients in the Reblozyl arm vs 46% of those in the epoetin alfa arm achieved RBC transfusion independence for at least 12 weeks during weeks 1 to 24 and in 48% and 29% of patients, respectively beyond week 24.
Regarding safety, the most common adverse effects occurring in more than 10% of patients included diarrhea, fatigue, hypertension, peripheral edema, nausea, and dyspnea.1
Connect With Others for Support and information
CancerConnect was the first social network created for people with cancer. Founded by oncologists to support MDS patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating MDS from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References:
- A Phase 3, Double-blind, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo for the Treatment of Anemia Due to the IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions. Available at . Accessed February 2020.
- Santini V, Fenaux P, Zeidan AM, et al. Overall survival and progression-free survival of patients following luspatercept treatment in the MEDALIST trial. Presented at ASH 2022; December 10-13, 2022. Abstract 1774.
- https://old-prod.asco.org/about-asco/press-center/news-releases/luspatercept-improves-anemia-and-reduces-reliance-blood
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US FDA approves Bristol Myers Squibb’s Reblozyl (lusatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes who may require transfusions. News release. Bristol Myers Squibb. August 28, 2023. Accessed August 28, 2023.
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Platzbecker U, Porta MGD, Santini V, et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet. 2023;402(10399):373-385. doi:10.1016/S0140-6736(23)00874-7
