MDS 2023 | Outcomes & promising treatment options following HMA failure in patients with HR-MDS

So, patients that have high risk MDS and fail hypomethylating agents, are in a very difficult place. Unfortunately, once patients fail either of the hypomethylating agents, whether it’s azacitidine or decitabine, they have a very poor prognosis and poor overall survival of four to six months. As of this day and age, we actually do not have any FDA approved therapeutic options for patients that fail azacitidine or dacogen. In addition to this, the biology of their disease also changes significantly at the time that they relapse. They have new mutations, they have more proliferation of more aberrant or worse clones, they may have different cytogenetics. So, I would say that a disease evaluation again at the time of relapse is also important to be able to offer the appropriate therapies. So, in the realm of therapies, what we actually do have is probably several clinical trials in frontline high-risk MDS as well as in relapsed /refractory high-risk MDS. Of the studies that are currently accruing patients, I think some of the promising results we are hearing about them here at this meeting in the MDS Foundation, but venetoclax and its combination with the HMAs looks to be very promising. We have several agents in development, such as the CD47 targeting drug magrolimab and several others. Also, those that are mutation specific like the IDH inhibitors and having different approaches that could be targeting specific mutations versus mutation agnostic approaches will probably give us the best chance of success in this difficult to treat patient population.