Switching Between Therapies in Myelofibrosis

EP: 1.Overview: A 67-Year-Old Man with Primary Myelofibrosis

EP: 2.Myelofibrosis and the COMFORT Trials

EP: 3.Myelofibrosis and its Clinical Phenotypes

EP: 4.Available Treatment Options for Myelofibrosis

EP: 5.Pacritinib in Myelofibrosis

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EP: 6.Switching Between Therapies in Myelofibrosis

EP: 7.Assessing Treatment Response in Myelofibrosis

EP: 8.Challenges in Treating Myelofibrosis

Case: A 67-Year-Old Man With Myelofibrosis

Initial presentation

RF is a 67 y/o man who visits his primary care physician for his yearly checkup. He reports having fatigue and bone pain for the last few months. More recently, he’s been complaining of abdominal discomfort which he thinks is probably related to the big Thanksgiving dinner party, he and his wife hosted.

He enjoys spending time working on antique cars in his garage, but his wife says he becomes tired after just an hour.

RF has not noticed any changes in his eating habits, but his wife mentions he doesn’t eat as much as he used too. Upon examination, RF has lost close to 13 lbs. since this last yearly exam.

PMH:

Primary myelofibrosis diagnosed about 1 year ago

Diabetes (controlled with diet and exercise)

COPD

SMH: Smoked 3 packs/day but quit 5 years ago; he drinks occasionally

PE: abdominal exam reveals spleen palpable 5cm below left coastal margin, visible bruising

Initial Labs/Workup:

Platelet count: 184 x 109/L

Hgb: 10g/dL

WBC: 34 x 109/L

Bone Marrow Biopsy

Shows an increase in megakaryocytes

Bone Marrow Fibrosis

Megakaryocyte Atypia

Molecular testing

JAK-V617F mutation: positive

Initial treatment:

Patient was started on ruxolitinib 10mg BID when initially diagnosed

Current Presentation/Labs:

One year later, RF reports increasing fatigue and abdominal pain

Current Labs:

Platelet count: 57 x 109/L

Hgb: 8g/dL

WBC count: 29 x 109/L

Raajit Rampal, MD, PhD: Let's talk a little bit about switching medications. We've talked about data for fedratinib and we've talked about data for pacritinib. Pacritinib can be used at a full dose of 200 mg twice daily in this patient's case if one were to switch therapies. Again, for the PERSIST2 data that we talked about, it does apply to a scenario like this, where a patient has had prior exposure to a JAK inhibitor and is now having progressive symptoms. In fact, this is also now in the NCCN [National Comprehensive Cancer Network] guidelines, so something important to keep in mind. Let's say we were to switch this patient to pacritinib as per the PERSIST2 data. Do we need to think about a washout period? To answer that question, we have to think a little bit about the pharmacokinetics of ruxolitinib. Ruxolitinib is a twice-daily drug with about a 6-hour half-life. It is not unreasonable to simply have the patient stay on ruxolitinib and start pacritinib the following day if one was going to switch therapies. Even if there is some degree of overlap of the drugs, it's not likely to be prohibitively myelosuppressive. One does not have to wash out the drug per se before starting the next drug. How do you choose what to start with? As we talked about a moment ago, we have new JAK inhibitors that are recently approved and have been studied in this particular scenario in patients who have failed therapy. But it's important to also remember to think about other possibilities, including clinical trials. There is an abundant number of trials currently in myelofibrosis for patients who are having evidence of progression or treatment failure on ruxolitinib, number 1. And number 2, we always have to think about allogeneic stem cell transplants. Of course this is the only curative therapy that we know of for this disease. In a patient like ours, who's relatively young—he's 67—and provided that he doesn't have prohibitive comorbidities such as lung function—an air impairment or cardiac impairment—a transplant could certainly be thought about as the next line of the therapy, in this case. But it depends on whether or not the patient is a candidate, whether or not the patient has a donor, and whether or not the patient actually wants to go through with the stem cell transplant. These are some of the factors that need to be considered when choosing the next line of therapy. Of course, none of these are mutually exclusive. It is also not unreasonable to try to better control the patient’s symptoms by switching them to an alternative JAK inhibitor and then proceeding to stem cell transplant if all these other factors we talked about a moment ago are met.

Transcript edited for clarity.