Two studies suggest luspatercept reduces need for blood transfusions

<p class="article-intro">Two phase III clinical trials show luspatercept to be safe and effective at reducing the need for blood transfusions. The studies focus on patients with beta thalassemia and myelodysplastic syndromes, respectively.</p> <hr /> <p class="article-content"><p>Beta thalassemia is a genetic blood disorder characterized by reduced production of hemoglobin, which is associated with life-threatening complications such as severe anemia and organ damage. Although new treatments have emerged in recent years, including curative gene therapies, blood transfusions remain the standard of care and most accessible treatment for a vast majority of patients. Many patients require transfusions every few weeks.<br /> Luspatercept is designed to increase the amount of healthy red blood cells by interfering with signals that suppress red blood cell production, thus improving patients&rsquo; ability to manufacture their own red blood cells and reducing the need for transfusions.<br /> The phase III trial BELIEVE enrolled 336 adult patients with beta thalassemia. Participants were mostly young, with a median age of 30 years, and required a median of six units of blood over a 12-week period before the trial. Two-thirds were randomly assigned to receive luspatercept and one-third received a placebo, both administered via an injection every three weeks.<br /> The researchers tracked the number of units of blood each participant required over the course of 48 weeks (about 11 months). The results show those taking luspatercept were 5,8 times more likely to reach the primary endpoint (a 33 % reduction in the number of units of blood needed during the study period) compared with those taking the placebo. By the final quarter of the trial, about 20 % of patients overall had cut their number of transfusion units by one-third or more, and 10 % of patients had cut their transfusion units by half or more.<br /> &bdquo;This new approach can totally change the quality of life for the patient. In addition, even for those who don&rsquo;t become completely transfusion independent, reducing transfusions can reduce associated comorbidities‟, said lead study author Maria Domenica Cappellini, of the University of Milan in Italy.<br /> Reported adverse events included bone pain and thrombotic events, such as stroke, but the rates of these events did not differ significantly between patients taking luspatercept and those taking the placebo.<br /> Genetic variation is known to affect the severity of beta thalassemia, so it may also affect the efficacy of treatments. The researchers plan to further analyze the data to determine whether genes or other factors affect how patients respond to luspatercept.</p> <p>Myelodysplastic syndromes (MDS) are a type of bone marrow cancer in which the bone marrow fails to manufacture enough healthy blood cells. Patients with higher-risk forms of the disease often develop bleeding, infections, or acute myeloid leukemia. Among those with lower-risk MDS, anemia is the most common subtype of low blood count and causes debilitating symptoms for many patients.<br /> Available anemia drugs only work for about one-half of patients with lower-risk MDS-related anemia and about one-quarter of those who are dependent on red blood cell transfusions. Patients who do not respond to these drugs or have adverse reactions to them may require frequent blood transfusions to boost their supply of red blood cells and hemoglobin.<br /> Red blood cell transfusions increase hemoglobin only temporarily, and frequent transfusions are costly and time-consuming. They can also lead to iron overload, especially in the heart and liver.<br /> The MEDALIST trial enrolled 229 adult patients with low, very low, or intermediate-risk MDS with ring sideroblasts. All patients had either failed to respond to available anemia drugs or were ineligible for treatment with such drugs, and required red blood cell transfusions at least every one to two months. Two-thirds were randomly assigned to receive luspatercept and one-third received a placebo, both administered via an injection every three weeks for at least six months.<br /> More than one-third (38 % ) of patients receiving luspatercept and 13 % of those receiving a placebo achieved the primary endpoint of at least eight weeks without a need for a red blood cell transfusion. 28 % of patients receiving luspatercept and 8 % of patients receiving a placebo achieved the secondary endpoint of at least 12 weeks without transfusion. Overall, 53 % of patients experienced either a significant reduction in the number of transfusions required or an increase in hemoglobin levels even without transfusions, compared with 12 % of patients receiving placebo.<br /> The most common reported adverse effects with luspatercept treatment included fatigue and muscle pain, though it is difficult to determine whether these effects were related to anemia or to the drug itself. It is also unclear whether the drug would offer benefits for patients with higher-risk MDS or those without lower-risk MDS without ring sideroblasts, researchers noted, since only low- and intermediate-risk patients with ring sideroblasts were included in the trial.</p> <p><br /><strong>References:</strong><br />Cappellini MD et al.: The BELIEVE-trial: Results of a phase III, randomized, double-blind, placebo-controlled study of luspatercept in adult beta-thalassemia patients who require regular red blood cell (RBC) transfusions. ASH Annual Meeting 2018, abstract #163<br /> Fenaux P 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. ASH Annual Meeting 2018, abstract #1</p></p>