Biomarker Analysis and Patient-Reported Outcomes from COMMANDS Study in MDS

Opinion
Video

An expert on MDS reviews the biomarker analysis and patient-reported outcomes from the COMMANDS study as well as long-term outcomes from the MEDALIST study.

This is a video synopsis of a discussion featuring Gary J. Schiller, MD, chief of the Hematological Malignancy/Stem Cell Transplantation program at the David Geffen School of Medicine at UCLA Health Jonsson Comprehensive Cancer Center.

In the study by Hayati et al., bone marrow morphology was assessed in patients treated with luspatercept for MDS-associated anemia. As shown previously, luspatercept significantly improves erythroid response versus placebo and erythropoiesis-stimulating agents (ESAs) by weeks 24 and 28.

Here, a significant increase in erythroid precursors was seen in marrow with luspatercept. Downregulation of inflammatory mediators interleukin (IL)-1, IL-1R, interferon, and IL-6 occurred, along with decreased anti-inflammatory IL-10 signaling. The authors conclude luspatercept improves erythropoiesis and decreases bone marrow inflammation in MDS. However, it is unclear if expanded erythropoiesis is from the neoplastic clone or normal polyclonal cells since cytogenetic/molecular studies were not performed.

In another study, Oliva et al. examined patient-reported outcomes from the phase 3 MEDALIST trial randomizing lower risk, transfusion-dependent MDS patients not previously treated with ESAs to luspatercept versus epoetin alfa. As published, luspatercept led to significantly higher transfusion independence rates. Here, quality of life by EORTC-QLQ-C30 instrument was a secondary objective.

As expected, quality of life improvement was superior with luspatercept versus epoetin including sustained effects. However, it is unclear if effects were limited to responding patients with decreased transfusion dependence/independence or accrued regardless of measurable erythroid response. Longer follow up and more granular data are needed to determine if potential anti-inflammatory effects of luspatercept increase quality of life beyond directly improving anemia.

In an extension study, Santini et al. evaluated longer term outcomes of luspatercept beyond the original MEDALIST trial. Over half of lower risk, ESA-refractory/relapsed MDS patients treated with luspatercept for >2 years maintained red blood cell transfusion independence, some for over a year with no significant new safety signals.

*Video synopsis is AI-generated and reviewed by Targeted Oncology editorial staff.

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