Assessing Treatment Response in Myelofibrosis

EP: 1.Pathophysiology of Myelofibrosis

EP: 2.Symptom Assessments in Myelofibrosis

EP: 3.Risk Stratifying Patients With Myelofibrosis

EP: 4.Treatment Planning and Myelofibrosis

EP: 5.Stem Cell Transplants in Myelofibrosis

EP: 6.Pharmacotherapy for Myelofibrosis

EP: 7.Approaching a Case of Primary Myelofibrosis

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EP: 8.Assessing Treatment Response in Myelofibrosis

EP: 9.Second-Line Treatment Options for Myelofibrosis

EP: 10.Second-Line Therapy for High-Risk Primary Myelofibrosis

EP: 11.Individualizing Therapy for Patients With Myelofibrosis

EP: 12.Optimizing Therapy for Patients With Myelofibrosis

EP: 13.Advances in the Treatment of Myelofibrosis

John Mascarenhas, MD: Let's say you embark on treatment and 80% of the participants said ruxolitinib and I think we would all agree, but how do you define what response to treatment is or an adequate or reasonable response?

Aaron T. Gerds, MD: Raajit, is there a magic formula? Do you follow [International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria]? Do you have a handy tape measure that you have to measure something? What do you do to measure response?

Raajit K. Rampal, MD, PhD: It's a great question and we've got to separate what we do in clinical trials vs what we actually do practically speaking. Look, it depends to some degree on what the treatment goals are. Fundamentally, one of the treatment goals we would all agree on is making the patient feel better. Certainly, using something like the total symptom score as a utility in this setting and on the other hand, just talking to the patient and getting that assessment. At the end of the day, really what makes a difference? If we're thinking about this more broadly, let's say, we're talking about a patient who we are thinking should go to stem cell transplant, does making them functionally feel better, make a difference? Of course, and that factors into stem cell scoring systems and whatnot but things like the spleen size there do probably make a difference. We at least have some vague notion that the smaller the spleen is going into transplant, the better. Where exactly the cutoff is I don't [know]. We could debate that but that becomes perhaps a more practical or objective measure that one would have to think about as a response if this is a patient who's going to transplant. But on a high level, let's say if we have a patient who is not a transplant candidate, if their spleen shrinks enough that they feel comfortable and that their symptoms are improved, I think that is a response.

Aaron T. Gerds, MD: It's a shame that John's not here because his favorite thing to go on about is the patient global impression of change. Do you feel better, worse, or the same, as a treatment goal and I think it's so simple. It's hard not to use.

Srdan Verstovsek, MD, PhD: I would add that I agree 100% but on top of it, I would like these factors to be controlled as much as possible by some measure. If we go by the questionnaire, is it whether it's complicated or maybe MPN 10 or a global impression of the quality of life improvements. Why not aim for the best you can get? Both the quality of life and the new spleen reduction, so that it will last longer. That's my goal. I want them to feel much better for as long as possible and that means optimizing the care. Making the spleen as small as possible, improving the quality of life, as much as possible. That is probably [more] reasonable than the goal of care.

Aaron T. Gerds, MD: The question is when do you consider changing therapies? Is it when the MPN 10 goes up by 6 points, when the spleen jumps out of the belly, or what are some things that you look for to consider changing therapy?

Srdan Verstovsek, MD, PhD: Well, it's difficult to continuously do the questionnaires or do the measurements of the spleen biopsy or [CT] scan so it's the old-fashioned way. Talking to the patients, understanding whether there is a benefit, palpation of the spleen, and looking at the weight, for example. My goal would be to maintain that benefit even if it's slowly going away by adding another agent to the JAK inhibitor that I'm using before I change. I would perhaps go to combinations. You mentioned thalidomide. There are a number of investigational agents that are being tested, inhibitor pathways, a kinase inhibitor, and a direct cell inhibitor. Maintaining that response as long as possible. We talked about hydrea. We can also talk about hypermethylating agents. In addition, if the blood starts to grow up, anemia drugs like luspatercept. These are all possibilities for me before you would actually say, "Enough is enough. Let's change". Or use of pacritinib that is coming as an investigational agent or patient without platelets. That would be my first choice if I had it today. I don't have it yet but hopefully in the future. Then the second line after the optimization of the care to the global benefit, to the maxim, and not to say early enough or too soon to say "Oh, enough. Let's go to the second line." So I would expand on that first line for as long as possible before I change.

Transcript edited for clarity.