Monitoring Strategies in Myelofibrosis

Shared insights on monitoring strategies for myelofibrosis, including important considerations for patients receiving treatment with JAK inhibitors.


Pankit Vachhani, MD: The monitoring strategy for patients with myelofibrosis has to be personalized. That said, generally speaking, every 2-to-4-month visits are sufficient for most patients. Some cytopenic patients may need more visits or laboratory tests, plus/minus transfusions. We don’t routinely get bone marrow biopsies or spleen volume or length assessments on routinely treated patients, let’s say outside of physical examination for spleen volume or spleen length assessment. Of course, the picture is evolving, and investigations may be needed for an individual patient should the situation progress or dynamically change. Also, depending on an individual patient’s scenario, one may want to consider getting an echocardiogram [EKG] or doctor examination to evaluate for let’s say, pulmonary hypertension or portal hypertension, or ascites. These are all known complications of myelofibrosis.

Naveen Pemmaraju, MD: In terms of monitoring our patients at the level of the clinic with myelofibrosis, there have been a couple of new insights that I think have helped our practices around the world. I would say No. 1 is many of us try to measure the MPN [myeloproliferative neoplasm] symptom burden and as systematic of a way as possible. Obviously, in clinical trials, we use the formal measures, so the MPN-TSS [Myeloproliferative Neoplasms Total Symptom Score], but many of us are trying to do something similar to or identical to what’s on the clinical trials. And I think that’s important because it gives a way to quantify the subjective, to really give a way to measure for our patients over time what’s going on with the MPN symptom burden.

The second aspect, of course, is a lot of us use blood tests and bone marrow, but I think many of us have been a bit more cautious with using routine or serial bone marrow biopsies. Again, those are usually built into clinical trials, especially with newer agents, but in the off-protocol commercial setting, standard of care setting, I think it’s very important to do a bone marrow biopsy at diagnosis as required by the WHO [World Health Organization] and other diagnostic entities. But then at the follow-up, especially in a patient who’s doing well, there is a movement now to potentially do fewer bone marrow biopsies unless and until there’s a need to do it, a change of status, etc.

Then finally, I think the most important thing in the MPNs for many of our patients is the history and physical. So going back to the basics, yes, measurement of spleen size, etc, as we’ve always known, but I think talking to our patients. The last 3 years of the pandemic have reminded us that these interactions— whether they’re done remotely or in person with the patient, with the nurse practitioner, the APP [advanced practice provider], with the physician, because now we have a whole provider team, the pharmacist—are very important in the care of these oral lifelong indefinite therapies, that all members of the health care team have regular interactions and to see what’s happening over time. And I think a lot of that can be uncovered with the conversations. I call it the story behind the story, what’s happening behind the scenes with the patient. You want to have a flavor of that. I think that you can determine a lot about fatigue and energy levels, itching, pruritus, neuropathy, some of these MPN symptoms that may or may not necessarily come up in a quick discussion.

I think frequent interactions with multiple members of an MPN health care team have been a model that many of us have adopted. And it’s a multidisciplinary team: pharmacists, nursing, PAs [physician assistants], advanced practitioners, physicians, the community or local physician liaison with the academic clinical trial physician. There’s a lot going on with all of that. I think communication and frequent interactions as indicated for each case are helping to determine the course of monitoring and looking for progression in our patients.

Aaron Gerds, MD: When considering different JAK inhibitors for an individual with myelofibrosis, I think there are a couple of things you want to consider. One is certainly the platelet counts, and that’s what the package inserts on each of these drugs focus on. Ruxolitinib has been the standard JAK inhibitor for many years and remains an important piece of the treatment landscape. I certainly would consider ruxolitinib in a patient who is symptomatic from their myelofibrosis and has relatively preserved blood counts, platelet counts over 100,000, and not very anemic, if anemic at all. That is the ideal candidate for ruxolitinib, and ruxolitinib in these patients has a pretty favorable adverse effect profile. The big thing to monitor with ruxolitinib would be lowering of the blood counts, development of anemia and thrombocytopenia. We often talk about the increased risk of nonmelanoma skin cancers and precancerous skin lesions and an increased risk of developing shingles over time. For anybody who’s had a history or risk factors for hepatitis or tuberculosis, you want to screen those folks prior to starting ruxolitinib because you can see the reactivation of hepatitis as well as tuberculosis, or TB.

The thing that isn’t monitored as much with ruxolitinib is cholesterol. Patients on ruxolitinib can have increases in their triglycerides and cholesterol levels. So, I think it’s prudent to check those every 6 months in patients on those treatments. That goes hand in hand with the weight gain and increased levels of leptin that we see for that medication. Fedratinib is a tougher one to start in the front line. Certainly, there are plenty of frontline data that are quite excellent, but in terms of adverse effect profiles, fedratinib has a bit less tolerability due to nausea and diarrhea owing to the inhibitory effect on FLT3. So, often fedratinib is reserved for second-line therapy, and in the JAKARTA2 study it performed splendidly after ruxolitinib.

In starting fedratinib, of course, you want to check thiamine levels prior to and during treatment as indicated by the package insert because there were reports of patients developing Wernicke-Korsakoff encephalopathy on the drug, although later this was found to be not due to fedratinib necessarily, as it does not inhibit the uptake of thiamine. But I think it’s prudent to check thiamine levels as well as start patients on thiamine supplementation. Of course, with the FLT3 inhibitory effect of fedratinib, you want to consider giving patients Imodium as well as an antiemetic prior to starting therapy in case those adverse effects do come up as they do quite often.

Pacritinib has carved a niche in the cytopenic myelofibrosis landscape, and so certainly for patients with platelet counts of less than 50,000, you would consider pacritinib as a frontline therapy. I would even say that in the second-line setting, considering pacritinib in patients with platelet counts as high as 100,000 as well is prudent based on the PERSIST2 study. With pacritinib, the unique things you want to watch out for are, again, GI [gastrointestinal] adverse effects, so giving patients Imodium as well as an antiemetic prior to starting treatment would make a lot of sense. Pacritinib does have a warning on the label for QTc prolongation, although in the PAC203 study, we did not see significant QTc prolongations, but it would make sense to check an EKG prior to starting pacritinib.

There were, over the development program of pacritinib, some increased risk of bleeding seen with patients on pacritinib as opposed to the best available therapy or other standards of care. So, in patients who have low platelet counts, you want to monitor them for bleeding and perhaps take caution in patients who are on blood thinners. As a class, JAK inhibitors are associated with a higher risk of major adverse cardiac events, so that’s worth keeping an eye on as well. This is not only seen in JAK inhibitors used for myelofibrosis but also for other indications like rheumatologic disorders. I think you can certainly use the platelet counts and blood counts in general, as well as the adverse effect profiles of each of these medications, to determine which one you might start first in a patient.

Transcript edited for clarity.

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