Jessica Lewis-Gonzalez, PharmD, BCOP, discusses practical strategies for optimizing myelofibrosis care, emphasizing that baseline blood counts should guide initial therapy. For patients with severe thrombocytopenia, she notes pacritinib as the preferred agent given its FDA-approved indication, while momelotinib is often selected first for those with anemia due to its anemia-improving mechanism. She adds that ruxolitinib and fedratinib show the strongest data for spleen reduction and that clinicians must account for symptom burden, risk stratification, comorbidities, and potential drug-drug interactions when selecting and sequencing therapies.
Lewis-Gonzalez underscores the importance of planning dose adjustments before treatment begins—considering organ function, interactions, and performance status—and reassessing doses as toxicities emerge to balance efficacy and safety.
Pharmacy Times: What are the most common reasons patients discontinue JAK inhibitor therapy, and how can clinicians and pharmacists work together to address them?
Jessica Lewis-Gonzalez, PharmD, BCOP: I think the most common issue I see, especially when considering what most patients start with initially, is hematologic toxicities. Our patients often present with cytopenias, and these therapies can sometimes aggravate those cytopenias.
We also see non-hematologic adverse events such as gastrointestinal issues—nausea, vomiting, and infections—as well as joint discomfort and pain, all of which can significantly impact quality of life. Another major concern is loss of efficacy over time; some patients eventually lose their response to therapy, and at that point we have to consider switching treatments.
Clinicians and pharmacists can work closely together to address these challenges through proactive monitoring. This includes checking blood counts at every visit to track hematologic toxicities, assessing non-hematologic toxicities and offering both pharmacologic and nonpharmacologic interventions, and making dose adjustments based on lab results. Patient education is also critical—not only at the start of therapy, but through ongoing conversations to reassess symptom burden and re-educate patients on how to best manage side effects.
Pharmacy Times: When deciding between available JAK inhibitors, what clinical factors should guide therapy selection in myelofibrosis?
Lewis-Gonzalez: Right now, the biggest factor for me is baseline blood counts. For patients with thrombocytopenia, as I mentioned earlier, pacritinib is really the preferred agent, and that’s the specific FDA-approved indication—for patients with severe thrombocytopenia and myelofibrosis. For patients with anemia, we tend to reach for momelotinib first, since it helps with the anemia itself due to its unique mechanism of action.
We also need to think about symptom burden and spleen size. The data for ruxolitinib and fedratinib are the most impressive when it comes to spleen reduction. Beyond that, risk stratification, patient comorbidities, and concomitant medications all factor in, with particular attention to potential drug–drug interactions.
Pharmacy Times: How do pharmacists help manage dose adjustments, monitor for adverse effects, and optimize therapy for patients on JAK inhibitors?
Lewis-Gonzalez: When it comes to dose adjustments, I like to think of them as an upfront consideration before we even start a patient on therapy. This depends on their organ function, drug interactions, and overall performance status. We have to ask: are we going to do the patient more harm than good by starting at the full FDA-approved dose, or should we begin at a lower dose for tolerability and then increase as needed?
The same approach applies if patients begin experiencing toxicities—we always have to balance efficacy with safety. Monitoring for adverse effects is critical. Beyond that, we think about therapy optimization. Patients may experience disease progression or lose response to their current therapy, so sequencing, switching, and guiding providers on the next best option become essential. Supportive care is also a big part of this—making sure all supportive medications are appropriate, comorbidities are managed, and lab monitoring is consistently performed alongside these therapies.