Inside the Clinic: Myeloproliferative Neoplasms: Current and Future Standards of Care - Episode 10
A brief review of the historical use of systemic therapy in patients who present with myelofibrosis.
Pankit Vachhani, MD: Prior to the availability of JAK1 and JAK2 inhibitors, ruxolitinib, and fedratinib, the treatment choices for patients with primary myelofibrosis were very limited and weren’t the best in terms of slowing down the disease, contributing to a survival difference, or improving symptoms. The treatments being used for many decades prior to ruxolitinib approval were hydroxyurea and various interferon products. Hydroxyurea and interferon allowed for some cytoreduction, but the overall symptom responses were less than 10%, as noted in many studies. Also, these agents aren’t great at managing symptoms of myelofibrosis. We don’t really use these drugs in the age of JAK inhibitor therapies, but for a long time they were the backbone of treatment options.
In terms of treatment options besides JAK inhibitors, let’s not forget the very important role of allogeneic stem cell transplants, which are still the only curative option for patients with myelofibrosis, both primary and post–ET [essential thrombocythemia], post–polycythemia vera [PV] myelofibrosis. In an appropriate patient, I highly recommend referring them for a stem cell transplant earlier rather than later, even if the transplant occurs many years down the line. Finding a donor and making sure they’re a good transplant candidate is key. Our current drugs aren’t curative in that regard.
In terms of the differences between primary and secondary myelofibrosis and how we treat them, if we look at the approvals of ruxolitinib and fedratinib, various guidelines suggest using these drugs in different cases of myelofibrosis; there isn’t a differentiation. Primary myelofibrosis and post-ET, post-PV myelofibrosis are treated similarly in many regards. High symptom burden and intermediate-2, high-risk patients are treated with JAK1 and JAK2 inhibitor therapies. The key difference is in how we risk stratify these patients. As mentioned in a different segment, the risk stratification for post-ET, post-PV myelofibrosis should ideally be done using the MYSEC-PM [myelofibrosis secondary to PV and ET prognostic model] risk-stratification schema. For primary myelofibrosis, that could follow DIPSS [Dynamic International Prognostic Scoring System], IPSS [International Prognostic Scoring System], or DIPSS plus risk-stratification schemas.
Finally, I want to clarify a point. When we say secondary myelofibrosis in this context, we’re referring to post-ET, post-PV myelofibrosis and not the reactive cases of myelofibrosis. For example, autoimmune myelofibrosis, which would be treated dramatically differently, with steroids or other immunotherapies.
Transcript edited for clarity.