Dr Ravandi-Kashani on the FDA Approval of Luspatercept in MDS

Farhad Ravandi-Kashani, MD, Janiece and Stephen A. Lasher Professor of Medicine, chief, Section of Developmental Therapeutics, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

In August 2023, the FDA approved luspatercept for the treatment of anemia in adult patients with erythropoiesis-Stimulating Agent (ESA)–naïve very low– to intermediate-risk MDS who may require regular red blood cell (RBC) transfusions. The regulatory decision was supported by data from the phase 3 COMMANDS trial (NCT03682536). The open-label, randomized study investigated the use of luspatercept vs the ESA epoetin alfa. Luspatercept was shown to produce superior RBC transfusion independence (RBC-TI) and hemoglobin (Hb) increase vs epoetin alfa.

At the 2023 SOHO Annual Meeting, Guillermo Garcia-Manero, MD, of MD Anderson Cancer Center, presented data from the phase 3 trial, showing that the study met its primary end point of RBC-TI. Of the patients (n = 178) who were treated with luspatercept, 58.5% remained RBC-TI for 12 weeks or more with a concurrent mean hemoglobin increase of at least 1.5 g/dL, compared with 31.2% of patients treated with the ESA epoetin alfa (n = 178; P < .0001).

Anemia and transfusion dependence has been one of the biggest challenges issues associated with the use of ESAs in this patient population. Although they are considered standard treatment, Ravandi-Kashani explains, ESAs have limited efficacy. Therefore, having a new agent with a different mechanism of action that can elicit significant improvement in RBC-TI is an important step forward in this space, Ravandi-Kashani emphasizes. The COMMANDS trial demonstrated that luspatercept can be superior to ESAs in the frontline for in this subset of patients, he concludes.