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ASH 2025 | Novel treatment options for differentiation syndrome: the need for trials to assess efficacy
Yannis Valtis, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses novel treatment options for differentiation syndrome. Dr Valtis highlights various agents that may show efficacy, but emphasizes that clinical trials are needed to further evaluate. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
There is not much evidence and so a lot of what we are thinking about is rather speculative at this point and we really do need trials to assess kind of how these different agents will work. But what we know is that differentiation syndrome can be a pretty dangerous toxicity of some of the novel agents for acute myeloid leukemia. Specifically differentiation syndrome with menin inhibitors seems to be a little bit different than a differentiation syndrome we’re all familiar with from ATRA and from the treatment of APL...
There is not much evidence and so a lot of what we are thinking about is rather speculative at this point and we really do need trials to assess kind of how these different agents will work. But what we know is that differentiation syndrome can be a pretty dangerous toxicity of some of the novel agents for acute myeloid leukemia. Specifically differentiation syndrome with menin inhibitors seems to be a little bit different than a differentiation syndrome we’re all familiar with from ATRA and from the treatment of APL. And so there is a lot of interest in thinking about what other agents can we use. Of course, we all use steroids to both prevent and treat differentiation syndrome. And then other cytoreductive agents like hydrea and other agents can be used. But I think my specific interest in the field is that because I spend a lot of my time in cellular therapy and work on cell therapy patients, is can we take some of the agents that have been shown to work in the cell therapy context and bring them over to differentiation syndrome? And I would say the answer is I don’t know yet. I think this is a very interesting question, but I want to be very clear that we don’t have any evidence that these are going to work. I think that there are IL-6 blocking agents like tocilizumab and siltuximab that might have a role in the differentiation syndrome. There are interferon gamma blocking agents such as emapalumab that might have a role. There is anakinra, which blocks IL-1. And so all of those agents could have a role in the treatment of differentiation syndrome. I would say, based on current evidence, I don’t think we should be using those agents outside of a clinical trial. And certainly, we should only be considering their use in a biomarker-driven approach. So if the IL-6 is very high in a patient who is having differentiation syndrome, I think it’s very reasonable to consider an IL-6 blocking agent. But I wouldn’t do that without a biomarker-driven approach.
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