How do you approach MDS patients with low/very low risk IPSS-R but high risk mutations on NGS?

This a great question and one that I think will become more frequent in clinical practice. As it stands in my practice currently, I have been managing my IPSS-R low/very low-risk patients as I always have, with either observation, ESAs, or lenalidomide (in the case of those with del 5q). Age and comorbidities are also important since MDS is primarily seen in older adults who may not have the reserve to tolerate aggressive therapies or allogeneic stem cell transplants. However, as the IPSS-M (Ber...

Indeed, we often forget to distinguish between prognostic (that aim to assess the probability of health outcomes that are yet to occur) vs. predictive (that aim to estimate the probability of treatment effect) models. I believe that one of the leading causes of overRx in the contemporary clinical practice is due to neglect of this distinction. NGS testing is these days, used almost as often as CBC. Also, we should not forget that prognostic and predictive models are rarely externally validated (...