Rare Disease Report

Anemia Patients with MDS Benefit from Luspatercept in Transfusion Burden

DECEMBER 02, 2018
Kevin Kunzmann
A day after investigators presented phase 3 results showing luspatercept’s benefits for red blood cell (RBC) transfusion burden for patients with β-thalassemia, more data from the 60th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego, CA, have shown the investigative drug’s similar benefit for particular cases of anemia.

Results from the phase 3, randomized, double-blind, placebo-controlled MEDALIST Trial, show the TGFβ superfamily ligands-binding therapy reduces RBC transfusion burden in adult anemia patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS).

According to the study, currently available anemia therapies only provide benefit for about half of patients with a lower-risk MDS-related condition—and about one-quarter of such patients dependent on RBC transfusions. Those who are unresponsive or susceptible to adverse events associated with current therapies could require more frequent blood transfusion—which only temporarily boost RBC supply.

The need for costly, inconvenient, and potentially harmful transfusion are chronic, and a major issue, said lead study author Pierre Fenaux, MD, PhD, of Hospital Saint-Louis, Paris.

“With low hemoglobin levels, patients are tired all the time and have an increased risk of falls and cardiovascular events,” Fenaux said in a statement. “When you can improve hemoglobin levels, you really see a difference in quality of life.”

Investigators randomized 229 patients 2:1 to either subcutaneous luspatercept 1.0 mg/kg (1.75 mg/kg titration) or placebo once every 3 weeks for ≥24 weeks. Qualified patients were aged 18 years and older, with Revised International Prognostic Scoring System (IPSS-R)-defined MDS risk of very low, low, or intermediate, along with RS and the requirement of RBC transfusions. All patients were ineligible to receive erythropoiesis-stimulating agents (ESAs).

The study’s primary endpoint was RBC transfusion independence (RBC-TI) for ≥8 weeks between weeks 1 and 24. A key secondary endpoint was RBC-TI for ≥12 weeks between weeks 1 and 24.

Median patient age was 71 years (range 26 – 95 years), with 62.9% reported as male. Median patient time from diagnosis was 41.8 months, with overall baseline characteristics balanced between treatment groups. Median RBC units received by patients were 5, transfused over 8 weeks during the 16 weeks prior to treatment.

Of the 153 patients to receive luspatercept, 58 (37.9%) reached the primary endpoint for ≥8 weeks, compared to just 10 (13.2%) of the 76 patients to receive placebo (OR 5.1, P < .0001). In the key secondary endpoint, 43 (28.1%) reached RBC-TI for ≥12 weeks, versus just 6 (7.9%) of those receiving placebo (OR 5.1, P = .0002).

In assessing for safety, investigators found that luspatercept’s profile was consistent with that previously reported in the phase 2 PACE-MDS trial. The most common reported adverse event with the therapy included fatigue and muscle pain, though investigators could not confirm whether these effects were related to anemia or to the drug itself.

They concluded the investigative drug significantly reduced transfusion burden in the patient population, with generally good tolerance. That said, it was unclear whether luspatercept would offer similar benefits or tolerability for patients higher-risk MDS or those without lower-risk MDS with our RS, due to study exclusions.

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