The Importance of Symptomatic Improvement in MPN

In addition to improving spleen size and anemia, symptom improvement is very important to patients with myeloproliferative neoplasms (MPNs), said Ruben Mesa, MD, FACP, executive director of Atrium Health Wake Forest Baptist Comprehensive Cancer Center, president of Atrium Health Levine Cancer.

This transcript was lightly edited for clarity.

Transcript

Momelotinib was approved a year ago and showed symptom reduction for certain patients. Can you discuss these improvements and the thresholds for symptom improvement that should be used when evaluating new therapies?

Momelotinib was one of the first therapies approved with a phase 3 registrational study that had symptomatic improvement as the primary end point, with other important evidence of clinical benefit really as important, a kind of secondary end point, such as improvement in anemia and splenomegaly. This is a JAK [Janus kinase] inhibitor. There is data, both from the frontline and the second line, demonstrating improvement in the symptomatic burden these patients face, as well as improvement in spleen size and in anemia.

In the end, patients really can have 2 concrete benefits from a therapy. They can either live longer, they can live better, or both. Most things that we have are really either a surrogate of one or the other of those really most important end points and outcomes that a therapy can have. In this study for momelotinib, again using patient-reported outcomes, we're able to hear directly from patients the benefits that they experienced. Now, indeed, as we've done threshold work [with] patient-reported outcomes, the patient is really the judge and jury. What is symptomatic enough to benefit from therapy, to be on therapy, is very much assessed through the lens of the individual. We assess their symptoms both in aggregate, using an approach called the total symptom score, where we look at each of the individual symptoms, but as well as complimentary, looking at the worst symptom a patient has and is one able to achieve significant resolution or diminishment of that symptom.

So, I've used the example, of these methodologies, which can include a score of zero to 100 or in some of the tools, zero to 70. If you have 3 items, which each are a 10, and I have 10 items, which each are a 3, you may have a greater impact on your quality of life by having those items that are 10-out-of-10 type symptoms. Indeed, if someone has, let's say, itching, that is a 10 out of 10, that can be unbelievably disruptive, both for their lifestyle as well as their quality of life. Whereas a series of low-grade symptoms is not ideal, but sometimes is more tolerable than fewer but more intensive symptoms.