Luspatercept ‘Preferred’ Therapy in ESA-Naive Patients With Lower-Risk MDS-Associated Anemia

Luspatercept continued to show therapeutic benefit in transfusion-dependent, erythropoiesis-stimulating agent (ESA)–naive patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS), according to a study presented at the 2024 American Society of Clinical Oncology Annual Meeting, held in Chicago, Illinois, May 31-June 4.

Investigators, led by Amer Zeidan, MBBS, MHS, Associate Professor of Medicine at Yale Cancer Center, conducted the study in response to the lack of effective therapies that provide durable benefit in this group of patients.

In the study, the authors reported clinically meaningful responses of luspatercept treatment from patients enrolled in the COMMANDS trial.

“Luspatercept provided clinically meaningful outcomes, supporting its use as the preferred [treatment] for ESA-naive patients with [lower-risk] MDS-associated anemia,” Dr. Zeidan and colleagues wrote.

The open-label, randomized, controlled COMMANDS trial was conducted at 142 sites in 26 countries. It enrolled adults with MDS classified as very low, low, or intermediate risk per the Revised International Prognostic Scoring System. All patients were ESA-naive and required red blood cell (RBC) transfusions.

The new clinical benefit assessments reported in this study include the following:

• Achievement and duration of at least a 50% reduction in RBC units transfused over a period of at least 12 weeks (week 1-end of treatment)
• Transfusion burden during treatment (weeks 1-24)
• Time to first transfusion
• Achievement and cumulative duration of all separate episodes of RBC transfusion independence (RBC-TI) lasting at least 12 weeks
• Mean hemoglobin increase of at least 1.5 g/dL over weeks one through 24

As of March 31, 2023, the investigators found significant differences between the two treatment groups, including a reduction in RBC units transfused in the luspatercept group (83.0% patients achieved at least a 50.0% reduction in RBC units transfused over a period of 12 weeks or more) versus the epoetin alfa group (66.9%); longer time to first transfusion (155 days vs 42 days); and a mean hemoglobin increase observed in luspatercept patients compared with epoetin alfa patients (74.2% vs 52.5%; P<.0001).

“Significantly greater proportions of luspatercept versus [epoetin alfa] patients achieved improvements in [hemoglobin] levels, reduction in [transfusion burden] and RBC units transfused, and had durable RBC-TI responses,” according to the investigators.

Funding was provided by Celgene, a Bristol Myers Squibb company, in collaboration with Acceleron Pharma, Inc.

Reference

 Zeidan A, Platzbecker U, Giovanni Della Porta M. Clinical benefit of luspatercept treatment (tx) in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)–naive patients (pts) with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial. Abstract #6565. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.