Long-Term Data From COMMANDS Trial Show Reblozyl May Help Patients With Lower-Risk MDS Live Longer

Updated results from the phase 3 COMMANDS trial, presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, showed that patients with lower-risk myelodysplastic syndromes (LR-MDS) who were treated with Reblozyl (luspatercept) had a median overall survival that had not yet been reached after more than three years of follow-up. By comparison, patients who received the standard treatment, Epogen (epoetin alfa) — a type of drug known as an erythropoiesis-stimulating agent, or ESA — had a median overall survival of 46 months, or roughly three and a half years.

While the survival difference did not cross the threshold for statistical significance, the trend was consistent and meaningful, researchers said.

"This is the first time on a phase 3 randomized study that we see the separation of survival curves," said lead investigator Dr. Guillermo Garcia-Manero, a hematologist at The University of Texas MD Anderson Cancer Center in Houston. "It's showing that there is an impact on the natural history of the disease when treated with [Reblozyl]."

What Is Lower-Risk MDS?

Myelodysplastic syndromes are a group of blood cancers in which the bone marrow does not produce enough healthy blood cells. In lower-risk forms of the disease, patients often experience significant anemia — a shortage of red blood cells — which can make them dependent on regular blood transfusions just to maintain their quality of life.

For many patients, that means spending hours in an infusion center, sometimes once or twice a month, receiving units of blood along with pre-medications and careful monitoring. Over time, patients can become less responsive to transfusions altogether.

"It's actually a major deal," Garcia-Manero said. "Our patients — they may spend all day in some chair unit being exposed to these transfusions, plus the cost that the transfusions have."

What the COMMANDS Trial Found

The COMMANDS trial enrolled 363 patients with lower-risk MDS who had never received an ESA and who were dependent on blood transfusions. Patients were randomly assigned to receive either Reblozyl or Epogen.

With more than three years of follow-up now available, the updated results show that Reblozyl outperformed Epogen across multiple measures:

• Transfusion independence: 76.4% of patients on Reblozyl achieved at least 12 consecutive weeks without a transfusion, compared with 55.8% on Epogen.
• Long-term freedom from transfusions: 25.3% of patients on Reblozyl remained transfusion-free for two and a half years or more, versus 10.5% on Epogen.
• Duration of response: The median duration of transfusion independence was 184.4 weeks — roughly three and a half years — for patients on Reblozyl, compared with 95.1 weeks for those on Epogen.
• Hemoglobin improvement: 80.2% of Reblozyl patients achieved a meaningful increase in hemoglobin levels, compared with 58.6% of those on Epogen.

Fewer patients on Reblozyl progressed to higher-risk MDS — 3.3%, compared with 7.3% in the Epogen group.

No new safety concerns were identified during the extended follow-up period, and the drug's tolerability profile remained consistent with earlier reports.

Why This Matters for Patients

Garcia-Manero said the survival signal becomes even more compelling when viewed alongside data presented at the American Society of Hematology meeting in December 2024. That analysis found that patients in the COMMANDS trial who had slightly higher hemoglobin levels and a lower transfusion burden at the start of treatment responded especially well to Reblozyl — with response rates approaching 90% and a median duration of response that had not yet been reached.

Taken together, those findings are informing a new trial called ELEMENTS-MDS, which is testing whether starting Reblozyl earlier — before patients become transfusion dependent — could improve outcomes even further.

"What if we don't let these patients become so anemic that they become transfusion dependent, and we initiate these therapies early?" Garcia-Manero said. "Can we even make their prognosis better than what we show with COMMANDS?"

That trial has completed enrollment, and results are expected in the coming years.

What Patients Should Know

For patients currently living with lower-risk MDS, Garcia-Manero said the updated COMMANDS data reinforce that Reblozyl is now the leading first-line treatment option for anemia in this setting — regardless of specific disease characteristics like ring sideroblast status or EPO levels.

"I think there is a full angle to these results that are really transformative for our patients," he said. "It's indicating that a safe drug, early in the course of the disease, can really have a major impact."

Patients who want to learn more about Reblozyl or clinical trials in lower-risk MDS are encouraged to speak with their hematologist or oncologist about whether these options may be appropriate for their care.