By Dr. Luke Fletcher
Willamette Valley Cancer Institute & Research Center
Low-risk MDS had many exciting updates, starting with the COMMANDS trial. This study is an open-label randomized phase 3 trial comparing frontline luspatercept vs. erythropoietin stimulating agent (ESA) for those with low-risk MDS defined by IPSS-R, <5% bone marrow blasts, EPO levels <500 U/L (to correspond to responsiveness to ESA), transfusion dependent. Unlike prior studies and the current luspatercept approval, it was not limited to ringed sideroblasts/SF3B1 MDS. Patients were randomized 1:1 to injected luspatercept once every three weeks vs. weekly epoetin. The primary endpoint was the achievement of transfusion independence for 12 weeks within the first 24 weeks with a mean Hgb increase of ≥1.5 g/dL. Other endpoints of interest included hematologic improvement with erythroid response at least eight weeks, transfusion independence at 24 weeks, and safety.
178 patients were treated on the luspatercept arm, with 176 on the epoetin arm. 301 patients were included in the efficacy analysis, showing 58.5% (86/147) of luspatercept patients vs. 31% (48/154) of epoetin patients meeting the primary endpoint (P<0.0001). Moreover, HI-E was seen in 74.1% (109/147) of luspatercept patients and 51.3% (79/154) of epoetin (P<0.0001). In terms of duration of response, the median RBC-TI ≥ 12 weeks was significantly improved, 126.6 weeks in luspatercept group and 77 weeks in the epoetin group. Low rates of discontinuation due to treatment-emergent adverse events were seen in both groups, with a higher rate in the epoeitin arm in general, mainly due to ineffectiveness.
All in all, this represents an exciting potential step forward. While additional information on specific quality-of-life outcomes would be helpful, from clinical experience, it can be clear that fewer transfusions, in addition to improved anemia, can improve fatigue and energy and decrease the time toxicity of labs and blood transfusions for many MDS patients. This may represent a new standard of care for frontline.
Key Points:
- Luspatercept improved transfusion independence in comparison to current standard of care Epoetin (Erythroid stimulating agent)
- Safety profile similar to prior studies and overall tolerable
Reference:
1) Garcia-Manero G, Platzbecker U, Santini V, 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). J Clin Oncol 41, 2023 (suppl 16; abstr 7003). DOI: 10.1200/JCO.2023.41.16_suppl.7003
