ASH 2024 | Outcomes of patients with IDH1/2-mutated accelerated/blast-phase MPNs in the era of IDH inhibitors

Yeah, so I’ve had the privilege of leading a large multi-center retrospective analysis of patients with accelerated and blast-phase MPNs. We’re really focusing on how they do in the current era of therapy, so 2017 to the modern day. So within this cohort of about 200 patients, we have 35 that had an IDH1 or IDH2 mutation. There have been retrospective reports previously, including by our group, suggesting that these patients may have an excellent response to IDH inhibitor-based therapy and have durable long-term overall survival. So we wanted to specifically look at that question within our cohort of patients. 

So when talking about the entire cohort, median overall survival was less than a year, it was about 0.8 years. However, when you look specifically at the IDH1 or IDH2-mutated patients, we found a median overall survival of over two years. Part of that, we wanted to get a sense of, is this being driven by the therapy that they’re receiving? So we did stratify these patients based on frontline treatment approach. So we looked at intensive chemotherapy, HMA plus venetoclax, IDH inhibitors in the frontline setting, or HMA-based therapy that does not include venetoclax. And while there is no statistical difference in overall survival between those four arms, numerically, the patients that did the best were those that received HMA-based therapy without venetoclax or IDH inhibitor-based therapy, with our hypothesis being, given that MPNs are not a BCL2-dependent disease, venetoclax may not be offering the same sort of responses that we see in AML while still giving toxicity such as myelosuppression. Therefore, patients that are not getting intensive chemo or HMA-VEN may have better tolerability to therapy, and therefore they can stay on therapy. 

So we’re looking to dive into this further and get a sense of if there are other drivers of improved outcomes in IDH1 or IDH2 accelerated or blast-phase MPNs. That being said, these may be a silver lining in a very difficult to treat patient population who have historically been very, very underserved by the therapeutic options we have for them.

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