Luspatercept for Beta-Thalassemia May Reduce Transfusion Burden, Maintain QoL

Maria Domenica Cappellini, MD

The addition of luspatercept to best supportive care in patients was shown to reduce blood transfusion burden while maintaining quality of life measures in patients with β-thalassemia.

These findings from the Phase 3 BELIEVE trial were presented at the American Society of Hematology (ASH) 2020 Virtual Meeting.

A team led by Maria Domenica Cappellini, MD, University of Milan, Italy assessed the effect of luspatercept, a first-in-class erythroid maturation agent, plus best supportive care on health-related quality of life. Previous data from the same trial has indicated that the drug can provide a meaningful reduction in red blood cell transfusions.

Although long-term red blood cell transfusions may lead to iron overload and associated complications—thus affecting quality of life—reducing transfusion may increase anemia-related symptoms. Thus, it becomes necessary to simultaneously address the symptoms associated with β-thalassemia and decrease the long-term burdens of transfusions.

The investigators included a total of 336 patients. They randomized them 2:1 to receive luspatercept or placebo; further, all patients received best supportive care, which included long-term burdens of transfusions and iron chelation therapy.

At the outset of the study, patients were subcutaneously administered 1.0 mg of luspatercept or placebo with titrations up to 1.25 mg/kg every 3 weeks for ≥ 48 week.

Health-related quality of life was evaluated using both the generic 36-item Short Form Survey (SF-36) and the thalassemia-specific Transfusion-dependent Quality of Life questionnaire (TranQol). The investigators administered the questionnaire at baseline and every 12 weeks up to 48 weeks of treatment.

Thus, the primary analysis focused on changes from baseline between groups up to 48 weeks, which primarily consisted of TranQol total scores and Physical Health (PH) as well as the SF-36 Physical Component Summary (PCS), Physical Functioning (PF), and General Health (GH).

Following the study period, the total HRQoL evaluable population—or those who completed the questionnaires at screening and at ≥ 1 post-screening visits—was 212 (94.6%) in the luspatercept cohort and 104 (92.9%) in the placebo cohort.

They noted that baseline health-related quality of life scores were comparable to the US general population for most of the SF-36 domains. However, GH, Role-Emotional, and Role-Physical domain scores were below those of the general population.

Over the course of the entire treatment period, mean scores on all primary and exploratory domains were considered stable between the treatment groups.

“When considering responders to luspatercept, patients receiving luspatercept and achieving a ≥ 50% reduction in red blood cell transfusion burden over 12 weeks were significantly more likely than patients receiving placebo to have a clinically meaningful improvement in PCS (31.1% vs 16.5%; P = 0.024), and PF (30.0% vs 13.2%; P = 0.007) at Week 48,” the investigators wrote.

They also reported statistically significant differences for some SF-36 domains between patients in luspatercept and placebo cohorts achieving transfusion independence for any 8 or 12 weeks.

And finally, among patients who had achieved a ≥33% reduction in red blood cell transfusion burden reduction, the luspatercept cohort had a higher proportion of patients with improved health-related quality of life scores for all domains. However, Cappellini and colleagues did not find any statistical differences between the cohorts.

“Overall, the addition of luspatercept to best supportive care reduced transfusion burden while sustaining TranQol and SF-36 health-related quality of life scores over time through Week 48 compared with those receiving placebo,” the investigators wrote.

“Patients with transfusion-dependent β-thalassemia responding to luspatercept were more likely to achieve clinically meaningful improvements in health-related quality of life compared with placebo."

The study, “Health-Related Quality of Life Outcomes for Patients with Transfusion-Dependent Beta-Thalassemia Treated with Luspatercept in the BELIEVE Trial,” was presented at ASH 2020.