MPN Workshop of the Carolinas 2024 | Accurately assessing treatment response in PV and deciding when to switch therapies

So the response has a standard criteria that we’ve been using for years and actually it’s either using the ELN or LWGMRT criteria where we have what I simplifiy to say control of the counts and no significant splenomegaly, control of the symptoms to of course, it should be complete control of the symptoms, but I can easily say that none of the drugs are magic and people will have some symptoms, and a lack of adverse events, or actually the consequences, which are the vascular, thrombotic or arterial. 

Of course, there are certain circumstances where people have unprovoked events after surgeries or some other exposures which should not be basically counted as a disease related or a medicine failure, but this has to be all taken in context.

So control of counts primarily. There is, of course, a debate about how low the platelets should be, how the red cells need to be, but there is definitely a general consensus and a recommendation to keep hematocrit below 45%. And then the response does require a lack of phlebotomies. So patients need to have a normal count without phlebotomies that’s considered a complete hematologic response.

And then changing the therapies based on that, it’s also actually dependent. Of course, if somebody has a breakthrough vascular event that’s a to go, because that apparently looks like the treatment failed. And of course, if that was in a situation where the patient was off therapies for some reasons or was undertreated for some reasons, or could not just get the dose ramp-up because of side effects, that has to all be considered, whether there was a real failure or it was just undertreatment. 

And then uncontrolled counts is a little bit questionable. Of course, somebody who has increased white cells and is permanently requiring phlebotomies every month is not controlled with the available therapy that’s there, so that one definitely deserves switching. I would say phlebotomies three to four times a year could be acceptable in certain situations. Of course, we all like it with the complete response without any phlebotomies, but sometimes we just have to compromise, and if patients just cannot tolerate higher drugs, we can say hey you can have 1 or 2 phlebotomies, I don’t really mind providing everything else is being nicely controlled. 

So that’s something to look at and definitely being aware of the warning signs, right? Rising white cells, persistent uncontrolled red cells, symptoms that are significantly burdening and really stay with the patients with poor quality of life even despite being in controlled counts. Because sometimes it does happen that a patient has normal counts but is significantly symptomatic. And at that level, we sometimes even doubt is it a medication intolerance, is it the side effects profile? Is it just the disease burden? What’s going on? And then in that situation, definitely keep an eye to see whether the disease has progressed to myelofibrosis, which comes with increased symptom burden. But in that level, assessing the spleen size to see whether there’s any immature hemopoietic cells out there. Of course, repeating bone marrow based to consider whether there is more fibrosis, more clonal evolution, and looking at the blast percentage. Those are a standard assessments that somebody should basically be on the lookout for all the time.

I would say any patient that’s failed frontline therapy should be assessed by MPN experts or somebody who’s seen that, because it’s not rare that we have patients that are just being not really properly dosed, they just need a little twist and will just do perfectly fine on the same agent. They just need a determination. Are we progressing? Are we having just sufficient therapies? Are there any comorbidities? So those I would definitely at least consult online or reach out, send them to referral centers maybe. You know, a lot of the time it is just one consultation where the patient just needs to be seen and assessed and make sure, yeah, they are doing alright, no worries. Particularly if they are younger, because we have lots of PV patients that are young.