Monitoring Treatment Response in MF

Srdan Verstovsek, MD, PhD: Because the major problems with the myelofibrosis are related to bone marrow failure, low red blood cells, low platelets, then symptomatic splenomegaly and bad quality of life, we would like to look at those signs and symptoms in a relativity objective way. For the blood cell count and bone marrow failure to exemplify, this one is relatively easy, right? We do blood cell count monitoring frequently. We look at the platelets and we adjust the dose of medications where the platelet numbers. We have no medications to improve the platelets, but we need to be cognizant about other numbers because of the effect on the standard practice medications. For anemia, we measure the red blood cell count, but we also look at the transfusion requirement. It’s not only about hemoglobin levels, it’s also about the requirement for transfusions. For example, we would measure the transfusions that happen. The goals of therapy would be getting to transfusion independence. That is not possible for platelets, for example. We don’t have the therapies for that, but we may have some medications to help with the anemia.

For the symptoms and spleen, we would like to have widespread use of the questionnaire—MPN 10 [Myeloproliferative Neoplasm Symptom Assessment Form 10]—which consists of 10 questions that will objectivize the quality to refer the patients, which is endorsed by the NCCN [National Comprehensive Cancer Network] guidelines. That would give us a good sense of what is happening with the patient and where the patient needs the therapy. If the patient is on therapy, is it working? Is the quality of life getting better? Answering those questions will help us guide that aspect of the benefit. For the spleen, we would like to have objective measures by some kind of technique, like an ultrasound, CT [computed tomography], or MRI [magnetic resonance imaging]. Realistically, what happens with the spleen is we measure it by palpation. We basically endorse at least palpation, so we have some measurements in a clinical record of centimeters or inches so that we know what’s happening. There are different aspects of looking at different problems and trying hard to objectivize those problems. Certainly, follow them on and off therapy to see how things develop for good or bad, in a semi-objective way.

Aaron Gerds, MD, MS: When I’m monitoring treatment response in patients with myelofibrosis, particularly on JAK [Janus kinase] inhibitors, there are 3 things that I’m monitoring. One is the blood counts, 2 is the spleen size, and 3 is the symptom burden. These are the 3 things I check at every clinic visit. It’s really a matter of monitoring all 3 because patients can progress in a lot of different ways. Some patients, their counts might be fine, their spleen might not be changed much, but their symptoms get much worse, or the spleen gets larger independently, or the counts change. All those could be an indicator of progression or lack of response to the initial treatment, which could prompt you to switch your therapy. What therapy you choose next is often based on what you’re seeing within each of those 3 domains. Is it mainly a change in the counts? Is it mainly a change in the spleen size or symptom burden? That may say, “OK, we need to either adjust the dose of what we’re doing, or switch to a completely different therapy, or add another therapy on top.”

When a patient with myelofibrosis has been treated for a while, and on a therapy, and we think things are starting to change, again, I’m looking at these 3 domains: the spleen size, the symptom burden, and the blood counts. If it’s clearly a pattern of change visit-to-visit with any of those 3 domains, and we’re starting to see loss of improvement or loss of control, then that would prompt me to switch therapies, or within multiple domains at a single visit. If a spleen is 3- or 4-cm longer and their symptom burden went from a total score of 8 to 14, there’s clearly a lot of badness going on and we’re seeing a lot of progression, then we’ll be thinking about switching to another therapy.

There are few therapies we have readily available in the clinic today, and often, for many of my patients, that’s potentially switching to a clinical trial. Clinical trials are our ability to develop treatments for the future for the broader population, and by offering clinical trials, I can offer more options for my patients, particularly those who had prior treatment that is no longer working for them. Oftentimes we will sit down and say, “This is what’s going on with you. We’ve got these clinical trials. This one is trying to directly address what’s going on with you,” and we may pick that. Or sometimes there are other patients where we do switch to, say, a different JAK inhibitor that is already FDA [Food and Drug Administration] approved, or add on an erythropoiesis-stimulating agent, for example, when they become anemic.

Srdan Verstovsek, MD, PhD: If we have, in our practice, objective ways of measuring the anemia, thrombocytopenia, spleen, and symptoms through looking at CBC [complete blood count] transfusion requirements for anemia, palpation, and measurements with a type of a screen or ultrasound, for example, and the MPN 10 for assessment of the symptoms, then we will be able to objectivize the problem for the patients. While the patient is treated, no other therapy works. Knowing the baseline, knowing the improvements, the degree of improvements and the possible failure as it happens—all of these can be tracked with the proper assessment of how the patient is doing through these tools. Once we’re convinced through objective measurements that the spleen is growing, if the anemia worsens, transfusions worsen, platelets worsen, or symptoms are lost through these measurements, then it’s time to switch. In addition, many times, we have a problem with the toxicity of a given therapy. Let’s say we’re talking about ruxolitinib and fedratinib. They are myelosuppressive. If they are causing excessive anemia or excessive thrombocytopenia, that’s intolerance. Thus, we may not talk about the loss of response in this case; we may talk about intolerance or inability to provide the benefit. That’s another reason to switch.

Transcript Edited for Clarity