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Monoclonal Antibody Reduced Need For Transfusions in Low-Risk MDS

— Results suggest a "paradigm shift" in the treatment of anemia for these patients

MedpageToday

CHICAGO -- Patients with transfusion-dependent, low-risk myelodysplastic syndromes (MDS) needed significantly fewer transfusions when treated with luspatercept (Reblozyl) for anemia compared with the current standard of care, according to the randomized phase III COMMANDS trial.

Among over 300 patients who required red blood cell transfusions for anemia, 58.5% of those who received luspatercept achieved transfusion independence with hemoglobin increase versus 31.2% of those who received the erythropoiesis-stimulating agent (ESA) epoetin alfa (P<0.0001), reported Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center in Houston, during a press briefing ahead of the American Society of Clinical Oncology (ASCO) annual meeting.

Moreover, luspatercept -- a monoclonal antibody that modulates the transforming growth factor-beta pathway and increases erythrocytosis -- provided significantly longer duration of transfusion independence compared with epoetin alfa (126.6 weeks vs 77.0 weeks, HR 0.456, 95% CI 0.260-0.798).

Luspatercept was also more effective than epoetin alfa in achieving hematologic improvement-erythroid response at ≥8 weeks (an indicator of how much hemoglobin is increased in the blood; 74.1% vs 51.3%), and resulted in higher rates of ≥12-week transfusion independence (66.7% vs 46.1%) and 24-week transfusion independence (47.6% vs 29.2%).

"Luspatercept is the first and only therapy, at this point, to demonstrate superiority in a head-to-head study against ESAs in transfusion-dependent, low-risk MDS, and it should be considered a paradigm shift in the treatment of this group of patients with anemia," said Garcia-Manero. "I think the results of the support the use of luspatercept upfront in patients who are now transfusion-dependent with low-risk MDS that are naive for prior therapy."

Luspatercept is currently approved in the U.S. for patients with ring sideroblasts (RS)-positive low-risk MDS after ESA failure, or who are ineligible for ESAs, he noted.

When asked what the results of COMMANDS mean for patients with no ring sideroblasts, Garcia-Manero pointed out that the trial enrolled more RS-positive patients due to the fact that luspatercept is already approved for that intervention and "was not really powered to really see a big difference between ESAs and luspatercept in the RS-negative context."

While 64.8% of RS-positive patients achieved transfusion independence with luspatercept compared with 25.9% of those with epoetin alfa, the percentage of RS-negative patients who achieved transfusion independence was similar in the two groups -- 41.0% and 46.3%, respectively.

"Furthermore, duration of response -- which really affects our patients in a more significant fashion -- is actually in favor of luspatercept," he noted.

Specifically, duration of transfusion independence for RS-positive patients was 120.9 weeks with luspatercept versus 47.0 weeks with epoetin alfa (HR 0.626, 95% CI 0.361-1.085), while for RS-negative patients it was not estimable versus 95.1 weeks, respectively (HR 0.492, 95% CI 0.148-1.638).

"That together with the toxicity profile of the compound, and a drug that is easy to administer every 3 weeks, is probably why, in my opinion, this drug will become the standard of care ... regardless of whether [patients] are RS-positive or -negative," Garcia-Manero said. "So, I think there is going to be a paradigm shift for a majority of our patients."

Treatment‑emergent adverse events (TEAEs) of any grade were observed in 92.1% of the luspatercept group and 85.2% of the epoetin alfa group, with 4.5% and 2.3% of patients, respectively, discontinuing treatment due to TEAEs. Treatment‑related AEs were reported by 30.3% of luspatercept patients and 17.6% of epoetin alfa patients.

Progression to acute myeloid leukemia was reported in nine patients (four who received luspatercept and five who received epoetin alfa). Overall rates of death were comparable between arms during treatment and post-treatment.

The COMMANDS study included patients from more than 20 countries. Median age was 74 years, and most were white (80%) and men (56%). All participants had lower-risk MDS as classified by the revised International Prognostic Scoring System, and none had received previous treatment with an ESA.

Luspatercept was given by injection once every 3 weeks for at least 24 weeks, while those in the epoetin alfa group received injection once a week for at least 24 weeks. After median treatment durations of 41.6 weeks for luspatercept and 27 weeks for epoetin alfa, there were 301 participants included in the planned interim data analysis.

The primary endpoint was defined as transfusion independence ≥12 weeks, and a mean hemoglobin increase ≥1.5 g/dL within the first 24 weeks of treatment.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by Bristol Myers Squibb (BMS).

Garcia-Manero disclosed relationships with, and/or support from, AbbVie, Acceleron Pharma, Astex Pharmaceuticals, BMS/Celgene, Curis, Genentech, Gilead Sciences, and Novartis.

Primary Source

American Society of Clinical Oncology

Garcia-Manero G, et al "Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS)" ASCO 2023; Abstract 7003.