Rami Komrokji, MD, presents to the panel a second clinical scenario of a 74-year-old with cytopenic myelofibrosis.
Rami Komrokji, MD: Here’s another case with a slightly similar situation. [This patient is] 74 years old, so a little older now. They have constitutional symptoms, bone pain, and splenomegaly 4 cm below the costal margin. They present with that cytopenic profile of myelofibrosis [MF], with a hemoglobin of 8.1 g/dL and a platelet count of 42,000 per μL. How would you approach this patient as far as upfront therapy?
Jeanne Palmer, MD: We only have 1 option when the platelets are below 50,000 per μL. Pacritinib is what can help in this setting.
Rami Komrokji, MD: Absolutely. We now have the approval of pacritinib. We’re learning more about cytopenic MF. These cases have a peculiar clinical and biological phenotype. Those tend to have less JAK2 allele burden. They’re enriched to splicing mutations, somewhat similar to MDS [myelodysplastic syndrome]. They’ve been very challenging to manage up front. Sometimes in our practice, even at 74 years of age, if they’re in good shape with no comorbidities, we’ll bring up transplant as a potential therapeutic or curative option down the road.
But as far as the short-term strategies, because the patient is symptomatic, I’d probably think of a JAK2 inhibitor. To your point earlier, if the patient only had cytopenia, without the splenomegaly and constitutional symptoms, I wouldn’t go to JAK2 inhibitors. We still see that all the time, that just by the diagnosis of myelofibrosis, everybody gets a JAK2 inhibitor. In some cases, when it’s only cytopenia, that isn’t the right way to go with treatment.
Ruben Mesa, MD: Without question, there are some patients who have more of an MDS phenotype, with no splenomegaly and no symptoms. You want to be certain that you’ve got the right diagnosis, particularly if they’re triple negative, because they can appear very similar. You can have a bit of secondary fibrosis in MDS. This is a good exemplar case in that first, pacritinib doesn’t have to be in the second-line setting. That’s a critical takeaway. The label doesn’t specify front line or second line, and there are data from both. We just came from the ASCO [American Society of Clinical Oncology] annual meeting. Several years ago, I presented the PERSIST-1 study, which included patients with marked thrombocytopenia. It was a frontline study, and it was clearly a positive study. Clearly, that’s an important piece.
Second, and I’ve seen a bit of this already, when patients are thrombocytopenic, the prescribing doctor still wants to lower the dose because that’s how we have evolved with other JAK inhibitors. Use the full dose, use 200 mg twice a day in a patient like this. That’s one of the advantages of pacritinib. You can use the full dose, irrespective of the platelet count, which is critical. We’re going to learn more as things evolve.
At the ASCO meeting, [Aaron] Gerds, [MD, MS,] presented an analysis of the MOMENTUM study and other data that we had with momelotinib looking at individuals with platelet counts under 100,000 or under 50,000 per μL, because patients were eligible if they had a platelet count of greater than 25,000 per μL, and we saw similar efficacy and safety in both the thrombocytopenic and nonthrombocytopenic patients. That too has been approved and may be another option for a patient like this in the near future.
Jeanne Palmer, MD: I have a question. I’d be very interested to see how you guys handle this. Let’s say you have a patient who has a starting platelet count of 20,000 per μL. You start them on pacritinib 200 mg twice a day, and then they become platelet transfusion dependent. When you look at the package insert, it says that for clinically significant thrombocytopenia, you hold the dose and restart at a lower dose. I’m struggling with how to approach that because I feel like you need that JAK inhibition, especially if they have big spleens and things like that. How do you interpret that package insert data?
Ruben Mesa, MD: As I look at thrombocytopenia, you’re right, there are some folks who are transfusion dependent to begin with, and you put them on and you’re adding this benefit. They clearly have a worse prognosis if they’re platelet transfusion dependent. The key is that we know that we can use it safely. In some patients, the platelets will rise, and in some, they’ll remain similar. Going from 20,000 to 10,000 per μL isn’t that big a delta. I’d press forward. A patient who’s requiring platelet transfusions is a sicker patient. I’m still circling back, should we consider transplant? Are they accelerating and need some other therapy in the mix? But like all package inserts, they’re probably a bit more conservative than what we are in practice. I’d press on.
Rami Komrokji, MD: This has been very informative. I always learn more from these [discussions] because it makes me pause and think about how I practice.
Transcript edited for clarity.