Dr Komrokji on the Potential Implications of the COMMANDS trial in MDS

Rami Komrokji, MD, vice chair, Malignant Hematology Department, head, the Leukemia and MDS Section, Moffitt Cancer Center, senior member, the Malignant Hematology and Experimental Therapeutics Program, professor in Medicine & Oncologic Sciences, the College of Medicine, the University of South Florida, shares the potential clinical implications of data from the phase 3 COMMANDS trial (NCT03682536) of luspatercept-aamt (Reblozyl) in patients with very low– to intermediate-risk myelodysplastic syndromes (MDS) who have not received prior treatment with an erythropoiesis-stimulating agents (ESAs). 

The phase 3 trial investigated the efficacy and safety of luspatercept vs ESAs for the treatment of anemia in this patient population. Notably, data presented at the 2023 ASCO Annual Meeting showed that 58.5% of patients who received luspatercept achieved transfusion independence for a minimum of 12 weeks with a hemoglobin increase of at least 1.5 g/dL compared with 31.2% of patients who received ESAs, meeting the study’s primary end point of red blood cell (RBC) transfusion independence.

The FDA previously approved luspatercept in April 2020 for the treatment of anemia failing an ESA and requiring 2 or more RBC units over 8 weeks in adult patients with very low– to intermediate-risk MDS with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis. The data from COMMANDS could potentially support the shift of luspatercept to an early treatment line, Komrokji says.

Luspatercept is currently under priority review by the FDA for the treatment of anemia in patients with very low– to intermediate-risk MDS who have not previously received ESAs and who may require RBC transfusions.

If luspatercept is approved in a new indication, this approach has the potential of becoming the first step of care in the management of anemia in patients with MDS-RS, particularly in patients who require blood transfusions, Komrokji says. However, for patients without ring sideroblasts, more data will likely be required to help determine which patients would most benefit from receiving earlier treatment with luspatercept, Komrokji expands.

Another prospective study will further investigate luspatercept in lower-risk, ESA-naïve patients who are not transfusion dependent, Komrokji continues. This approach is reminiscent of what is currently done in practice, where treatment is generally started before patients become transfusion dependent to start treatment, he says. Overall, COMMANDS was a positive phase 3 trial that could help alter the MDS treatment landscape, he concludes.