Reblozyl May Be ‘The Standard of Care’ Now in Lower-Risk MDS, Anemia

Reblozyl (luspatercept) has become the new standard of care for patients with low-risk myelodysplastic syndromes (MDS) facing anemia (low red blood cell count), an expert explained in an interview with CURE®.

Dr. Guillermo Garcia-Manero of the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, led the phase 3 COMMANDS study comparing treatment with Reblozyl with treatment via epoetin alfa, a type of drug known as an erythropoiesis-stimulating agent (ESA), which stimulates the bone marrow to produce more red blood cells.

“In this study, it is very clear that this agent [Reblozyl] is superior to a standard of care in terms of improvement of [blood] transfusion needs, increasing levels of hemoglobin for a significant fraction of patients with MDS,” Garcia-Manero said during an interview with CURE®. “So, basically, in my opinion, this is now the standard of care for a large majority of patients with anemia [and] lower-risk MDS.”

The Food and Drug Administration (FDA) approved Reblozyl in 2020 for the treatment of patients with MDS who required red blood cell transfusions and had received treatment with an ESA. That approval was expanded by the FDA in 2023, based on the findings of the COMMANDS trial, to include the treatment of anemia in patients with very low- to intermediate-risk MDS who may require red blood cell transfusions and had not received an ESA.

LEARN MORE: Reblozyl Continues to Improve MDS Transfusion Independence

MDS encompasses many bone marrow disorders that involve the bone marrow not producing enough healthy blood cells, according to the MDS Foundation, which states on its website that most people are anemic when they receive an initial diagnosis of MDS. Signs and symptoms of anemia include fatigue, heart palpitations, shortness of breath and pale skin. Reblozyl, according to the National Cancer Institute, is intended to enhance the bone marrow’s red blood cell production.

COMMANDS enrolled 363 patients with MDS of very low risk, low risk or intermediate risk who had not been treated with ESAs and were, due to anemia, dependent on blood transfusions and treated with Reblozyl (182 patients) or epoetin alfa (181 patients).

The study’s primary goals included at least 12 weeks of red blood cell transfusion independence and a mean hemoglobin increase of at least 1.5 grams per deciliter in weeks 1 to 24 that was met by 60% of the Reblozyl group and 35% of the epoetin alfa group at median follow-ups of 17.2 months and 16.9 months, respectively.

At a median follow-up of 21.4 months in the Reblozyl group and 20.3 months in the epoetin alfa group, common grade 3 (severe) or 4 (life-threatening) treatment-emergent side effects that occurred among patients treated with Reblozyl (182 patients) were hypertension (19 patients), anemia (18 patients), pneumonia (10 patients), syncope (fainting; 10 patients), neutropenia (low count of neutrophils, a type of white blood cell; nine patients), thrombocytopenia (low platelet count; eight patients) and dyspnea (shortness of breath; eight patients) and MDS (six patients).

For the 179 recipients of epoetin alfa, common grade 3/4 treatment-emergent side effects included anemia (14 patients), pneumonia (14 patients), neutropenia (11 patients), MDS (10 patients), hypertension (eight patients), iron overload (seven patients) and COVID-19 pneumonia (six patients).

Researchers reported that the most common serious treatment-emergent side effects in both groups were pneumonia (nine in the Reblozyl group and 13 in the epoetin alfa group) and COVID-19 (eight and 10 patients, respectively), and one death, due to acute myeloid leukemia, was considered to be Reblozyl-related and reported at the time of the interim data analysis.

The findings of COMMANDS, Garcia-Manero said, have in turn led to the ELEMENTS-MDS trial evaluating Reblozyl among transfusion-independent patients with MDS with anemia. That phase 3 study, according to its listing on clinicaltrils.gov, is currently recruiting patients.

“Based on the [established] safety profile and the level of activity, we're moving into a large study looking at this drug [as] front[line treatment] in transfusion-independent patients with anemia,” he said. “That is actually where we think that these drugs will really, really work well, actually, when you have significant activity.”

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