CONFERENCE UPDATE: ASCO 2023

Luspatercept demonstrates superiority to epoetin-α in ESA-naïve patients with transfusion-dependent low-risk MDS: Interim analysis of the COMMANDS trial

ONCOLOGY HEMATOLOGY
27 Aug 2023

Study Design

Luspatercept has been previously proven to improve erythropoiesis in the MEDALIST trial and is beneficial to patients with low-risk myelodysplastic syndromes (MDS) with low transfusion burden, leading to an increase in mean platelet and neutrophil counts.1

The COMMANDS study was a global, phase 3, open-label, randomized trial designed to compare the efficacy and safety of luspatercept against epoetin-α for the treatment of anemia in erythropoiesis-stimulating agent (ESA)-naïve adult patients with transfusion-dependent low-risk MDS, as defined by the Revised International Prognostic Scoring System (IPSS-R).1 The patients were randomized 1:1 to receive luspatercept (n=178) 1mg/kg every 3 weeks (Q3W) or epoetin-α (n=176) 450IU/kg once weekly (QW).1 The composite primary endpoint was red blood cell (RBC) transfusion independence (TI) and concurrent mean hemoglobin (Hb) increase of ≥1.5g/dL.1 The secondary endpoints were hematologic improvement-erythroid (HI-E) response ≥8 weeks by the International Working Group (IWG) criteria, RBC-TI for ≥12 weeks, and RBC-TI at 24 weeks.1 The results were reported in the prespecified interim analysis of the first 24 weeks.

 

 

FINDINGS

 Primary endpoint:
  • The composite primary endpoint was RBC-TI ≥12 weeks with concurrent mean Hb increase of ≥1.5g/dL1

  • About 58.5% (n=86) of patients on luspatercept achieved the primary endpoint vs. 31.2% (n=48) in the epoetin-α group (p<0.0001)1

 Secondary endpoints:
  • The secondary endpoints included HI-E response ≥8 weeks by the IWG criteria, RBC-TI for ≥12 weeks, and RBC-TI at 24 weeks1
  • Significantly, more patients achieved HI-E ≥8 weeks in the luspatercept group with 74.1% (n=109) vs. 51.3% (n=79) in the epoetin-α group (p<0.0001)1
  • A significantly higher proportion of patients on luspatercept achieved RBC-TI for ≥12 weeks (66.7% vs. 46.1%; p=0.0002)1
  • Patients treated with luspatercept were more likely to be RBC-TI for ≥12 weeks (HR=0.456; 95% CI: 0.260-0.798) with a median time to RBC-TI ≥12 weeks at 126.6 weeks (95% CI: 108.3-NE), compared with the epoetin-α group at 77.0 weeks (95% CI: 39.0-NE)1
  • A significantly higher proportion of patients on luspatercept achieved RBC-TI for 24 weeks (47.6% vs. 29.2%; p=0.0006)1

 Safety:
  • About 92.1% (n=164) of participants in the luspatercept arm had treatment-emergent adverse events (TEAEs) of any grade compared with 85.2% (n=150) in the epoetin-α arm1
  • The rate of any-grade neutropenia was slightly higher with epoetin-α than luspatercept (7.4% vs. 5.1%)1
  • The rate of any-grade thrombocytopenia was higher with luspatercept than epoetin-α (6.2% vs. 1.7%)1
  • The rate of treatment discontinuation was lower with luspatercept than epoetin-α (43.8% vs. 59.7%)1
  • The safety findings with luspatercept were manageable and consistent with the established safety profile1

 

"Luspatercept is the first and only therapy that demonstrates superiority in a head-to-head study against ESAs, bringing a paradigm shift in the treatment of low-risk MDS associated anemia."

Dr. Guillermo Garcia-Manero
The University of Texas M.D. Anderson Cancer Center,
Houston, Texas, United States

Get access to our exclusive articles.