SOHO 2021 | Evaluating therapies in MDS
Andrew Brunner, MD, of Massachusetts General Hospital, Boston, MA, discusses the use and pitfalls of hypomethylating agents (HMAs) including azacitidine and decitabine, which are widely used backbone agents. Dr Brunner also describes the criteria used to assess in evaluating therapies for the treatment of myelodysplastic syndrome (MDS) such as the quantity and quality of life, and the depth of responses, as well as outlines how best to proceed following unresponsiveness to HMAs. This interview took place during the ninth annual meeting of the Society of Hematologic Oncology (SOHO 2021) congress.
Transcript (edited for clarity)
MDS is a tough disease. It’s hard when your bone marrow doesn’t work, and patients have complications arising from that, infectious bleeding complications, complications of anemia. I think cardiovascular complications is increasingly recognized as well. To that regard, one treatment remains the therapy of choice to prolong quantity and quality of life, and that’s azacitidine, or often substituted decitabine, a hypomethylating agent therapy...
MDS is a tough disease. It’s hard when your bone marrow doesn’t work, and patients have complications arising from that, infectious bleeding complications, complications of anemia. I think cardiovascular complications is increasingly recognized as well. To that regard, one treatment remains the therapy of choice to prolong quantity and quality of life, and that’s azacitidine, or often substituted decitabine, a hypomethylating agent therapy.
So far, we have not been able to unseat HMA therapy from its pedestal of treating patients. I think that there are some strengths to it. It’s tolerable. Most of our patients are older, we can get older patients onto it. The risk profile is a little different than some of the therapies we use for AML.
But that said, there’s a lot of underwhelming aspects to it. Only a minority of patients will get a response, and so certain trials have been developed to try to identify combinations or new therapeutic strategies that can increase the overall response rate. That can be meaningful for certain patients. I think we are starting to look at depth of response. If we can increase the number of people who respond from 15 to 20% up to 50 to 60%, then it would be more relevant to know what quality of response are those responses.
I think that there’s also an understanding that disease pre-transplant matters. We don’t know if we can treat somebody pre-transplant and modify their post-transplant risk, and that is something that I hope we can test prospectively as well. But we know that the disease burden right before transplant or shortly after transplant can be prognostic for how a patient does long-term.
I think the other main area where we are evaluating new therapies is how long patients can survive. Does the therapy, even if it has some medium improvement in overall response rate, if it bestows a better long-term survival rate, that would be a big impact for our patients who are on HMA therapy. The minority of them will be alive by five years, some estimates under 10%, and so if we can improve upon either of those, I think that that is still the primary effort of most of our research.
Because HMA remains kind of our backbone of therapies, a big unknown is what best to do once somebody stops responding to hypomethylating therapy, and that space is a very challenging and heterogeneous space for MDS. Patients generally have universally poor outcomes once they’ve stopped having a response to hypomethylating therapy, and so that is probably the one other very obvious area of need for the treatment of our patients with MDS. How do we come up with more effective ways to salvage a response or to recover a response once they’re no longer getting what they need out of hypomethylating therapy?
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