Expert Perspectives on Long-Term COMMANDS Findings

Expert Perspectives on Long-Term COMMANDS Findings

Experts review the longer-term COMMANDS trial data with a focus on durability of response and survival benefits in patients with lower-risk MDS. Key points highlighted include the 5-year survival advantage and the sustained transfusion independence achieved in many patients. While the trial was not designed to specifically analyze all molecular or cytogenetic subgroups, observations regarding response rates in patients with SF3B1 mutations vs those without are discussed. The data suggest durable responses across subgroups, though with nuanced differences in efficacy that warrant further study.

Panelists debate whether subgroup differences—particularly between SF3B1-positive and -negative patients—should influence frontline treatment decisions. Historically, some therapies have been more effective in SF3B1-positive populations, but the COMMANDS results suggest a broader applicability, including meaningful benefit in negative patients. This has shifted expert consensus toward positioning the novel agent as a strong frontline option, especially for those with SF3B1 mutations. Importantly, the duration of transfusion independence and quality-of-life improvement are emphasized as key clinical decision-making factors.

The discussion also addresses whether observed survival benefits are solely attributable to transfusion independence or whether additional “human-modifying” effects may play a role. Beyond improved hemoglobin levels, there may be systemic benefits such as reduced inflammation and improved cardiovascular outcomes that indirectly extend survival. While further mechanistic studies are needed, clinicians acknowledge the possibility of broader biologic effects beyond bone marrow modification alone. Ultimately, the panel agrees that the COMMANDS findings strongly support the use of this therapy as a frontline standard in appropriate cases of patients with lower-risk MDS, with potential implications for redefining disease modification in this population.