Hematologic Oncology Update, Issue 1, 2016 (Video Program)When to intervene in myeloproliferative neoplasms: Clinical indications for ruxolitinib
3:57 minutes.
TRANSCRIPTION:
DR SMITH: My big struggle in taking care of these patients is really when to intervene. And that’s the question we’re all struggling with as clinicians. And I’ve used blood counts. I’ve used performance status and symptomatic splenomegaly, or the development of symptomatic splenomegaly. And I’ve used a third criteria, which has been written about in lots of papers, but maybe some people don’t view it as a formal criteria. But that is the evolution of peripheral blood blasts. So when patients start to have these diseases and have cytopenias, I think they can be tracked and followed pretty carefully. When they start to have disease where they’re symptomatic from the disease and they start to show peripheral blasts, that makes me more anxious that their disease is really evolving. And we need to do some sort of significant intervention, because these patients really begin to carry a poor prognosis when we start to see those markers. DR LOVE: For a patient who had a fantastic response with MF to ruxolitinib but developed herpes zoster, what’s the issue there? DR SMITH: Yes. I think one of the recommendations out there is whether people should have shingles vaccines prior to getting this therapy. And that is a recommendation now, that if there’s time, the patient should be vaccinated with shingles vaccine because they are at increased risk for the reemergence of a herpes zoster infection when people are on these JAK2 inhibitors. DR LOVE: What about other JAK inhibitors? DR SMITH: The question out there from the biology is, which JAKs are the ones we need to inhibit, which ones are proliferative, which ones help suppress normal hematopoiesis? And so the effort to really study the biology is, can we isolate the JAK2 versus the JAK1 inhibition? And what kind of results do we see? Currently, there is some discussion that maybe inhibiting 2 might be too toxic or maybe we should need to save those for more aggressive cases of the disease. I mean, we certainly know the best that JAK2 inhibition should shrink spleens and can get rid of lots of side effects, itchiness and skin rashes and sometimes fatigue and B symptoms. So there can be a lot of quality-of-life improvements with JAK2 inhibition. It does cause lowering of blood counts, predictable lowering of blood counts. The platelets drop 20,000 or 30,000. You can understand what you’re getting into there. But it doesn’t necessarily fix all the blood count abnormalities. It doesn’t necessarily improve the anemia that you see. And certainly there have not been great studies to suggest that it alters the fibrosis pattern for a lot of patients. So again, symptomatic control is where we are with these. The question is, can JAK1 do better? Can combinations do better? Do you need to think about bringing in another type of TKI to help with that? One of the interesting combinations people talk about particularly for fibrosis, is, lenalidomide has some activity in fibrosis. And it has some activity, like it does in MDS, that it can improve red cell counts. So it can improve the anemia that’s seen in some of these diseases. The question is, are there combinations that would be tolerable of those drugs that might be able to be more effective in some of our patients long term? To be determined. |