Educational content on VJHemOnc is intended for healthcare professionals only. By visiting this website and accessing this information you confirm that you are a healthcare professional.

Share this video  

SOHO 2021 | The treatment protocol for higher risk MDS

Andrew Brunner, MD, of Massachusetts General Hospital, Boston, MA, describes the treatment protocol for higher risk myelodysplastic syndromes (MDS). Despite the absence of new drug approvals for the treatment of high-risk MDS, greater understanding into the molecular behavior of the disease and its dynamics has enabled the development of optimal treatment regimens. Dr Brunner explains the first step is the evaluation of transplant candidacy whereby patients ineligible for transplant undergo treatment primarily with hypomethylating agents. Additionally, patients with mutations such as FLT3 or IDH1/2 mutations can be put on mutation-specific treatment regimens earlier in the algorithm. This interview took place during the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.

Transcript (edited for clarity)

Although there have not been many new approvals in the treatment of high-risk MDS, we really are starting to evolve in how we approach that disease entity, both in clinical trials, but also just in our greater understanding of the molecular behavior of a disease and also our understanding of some of the dynamics of disease that we’ve somewhat borrowed from AML. I think that for many patients with MDS, what was known before is all the more clear, that transplant candidacy is a critical first step in assessing a patient...

Although there have not been many new approvals in the treatment of high-risk MDS, we really are starting to evolve in how we approach that disease entity, both in clinical trials, but also just in our greater understanding of the molecular behavior of a disease and also our understanding of some of the dynamics of disease that we’ve somewhat borrowed from AML. I think that for many patients with MDS, what was known before is all the more clear, that transplant candidacy is a critical first step in assessing a patient. For us, we really try to have almost all of our patients assessed by our transplant team because numeric age, for instance, is much less a barrier than it was in the past. It’s much more important to give patients a chance for evaluation because that’s really the best long-term treatment for most patients with MDS.

For those that aren’t transplant candidates, we’re still using hypomethylating agents primarily. And even for those who are, they may need some degree of cytoreduction before. I think there is a little bit of nuance that’s starting to emerge in MDS. One of those areas is molecularly driven therapies. Now, really we only have those that are largely more studied in AML, but the few patients with MDS with a mutation in IDH1, IDH2, or FLT3, sometimes those can be incorporated into early or later lines of therapy.

And then thinking about some disease entities as perhaps being more AML-like, I think a good example is NPM1 mutations in MDS. Again, although uncommon, they do respond very well to AML-like therapies, such as induction or azacitidine and venetoclax. And so while I determine whether or not somebody is a transplant candidate and prepare them for that undertaking, I’m also often thinking about some degree of treatment having methylating agents being our standard backbone, but with a lot more variation, perhaps depending on the molecular profile and also on the intent of the treatment for the patient. I think what we hope will happen is that that becomes even further nuanced if we get some agents that have, for instance, a clear improvement in overall response rate, compared to azacitidine monotherapy, perhaps we’ll want to get better response before something like a transplant or a survival benefit for azacitidine that would also influence how we treat patients. And I’m hoping that some of the Phase III studies that are underway will shed light on possible future avenues to that regard.

Read more...