ESH CML/MPN 2025 | Monitoring for and managing CV adverse events when treating patients with JAK inhibitors

It’s something that certainly we need to be mindful of. And I think so the first line therapy will be ruxolitinib across the country with second line, first or second line, momelotinib is now available since 2022. And then in the second line, you have fedratinib. So these are the three JAK inhibitors that are available. 

In terms of thrombotic risk and cardiovascular complications, I think with ruxolitinib, it’s important to highlight that there is a signal of increased cholesterol and increased lipids with the agent. So we know that it acts on the leptin axis, but it also acts on sort of lipid and cholesterol processing axis. So patients can have an increased cholesterol, which leads to risk of cardiovascular events. So I think it’s very important to either via GP, asking the GP to monitor this, or within the centre itself to check the cholesterol periodically on a patient, probably annually, to monitor this. 

But going beyond this I think there certainly is to be highlighted with momelotinib there is a proportion of patients at risk of what we call MACE, so major adverse cardiovascular events. This is more often in patients who have known cardiovascular history so what I would do is really caution a clinician starting this medication on somebody who has a known cardiovascular history to weigh up the pros and cons of starting momelotinib and if the patient is clearly stable without a recent cardiac event consider starting this, but monitor closely for any symptoms in that context. 

So if a patient experiences cardiovascular symptoms on momelotinib this is of course important to investigate immediately and if a patient experiences a significant adverse cardiovascular event on the agent, certainly if grade three you would require to interrupt the drug during this period and what I would recommend is to follow the advice as per the summary of product characteristics for momelotinib, and then maybe in discussion with a tertiary center when to restart the drug, depending on the resolution of the cardiovascular event in that context. There are cases reported additionally with fedratinib, but fewer cases. But this is still something I think across the JAK inhibitors to be aware of as a risk, although it’s still a relatively rare side effect.

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