Individualizing Therapy for Patients With 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

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

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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: Raajit, typically, when you treat someone for example with ruxolitinib [Jakafi], what is the expected duration of benefit and how do you plan in terms of lining up what the next agents might be for that patient?

Raajit K. Rampal, MD, PhD: I think it’s variable and there is the real-world experience data and the trial data from the comfort studies. I think roughly one has to start thinking that when you start somebody on ruxolitinib that the clock may start ticking. That there is going to be treatment failure potentially in 18 to let’s say 30 months or so. I think that’s the mindset one has to have when starting treatment. Some of what we think, from Srdan’s work, is predicated on the genetic profile of the patient. Having multiple mutations, such as ASXL1 [ASXL transcriptional regulator 1] mutations, may certainly predict a quicker time for treatment failure. All of those things need to be thought about carefully when initiating any type of therapy. Now, when you are thinking prospectively about a given patient and you are thinking or trying to factor into this idea that the JAK [Janus kinase] inhibitor may fail. Of course, what are the downstream things you think about? You can think about a transplant if that patient is transplant eligible, but I think the hope would be to get the patient to transplant before the ruxolitinib stops working. But now, we are entering an era as we’ve been talking about here with other JAK inhibitors. We have data for fedratinib [Inrebic] patients who have been on ruxolitinib previously. And certainly, there is about a third of patients [who] will have objective responses based on the JAKARTA-2 reanalysis. So that remains an option but as we’ve been talking about in a case scenario like this, pacritinib certainly could be a meaningful switch for a patient who develops cytopenia. I think unlike where we were 3 or 4 years ago, more roads are opening up here downstream for patients when and if they fail their therapy.

John Mascarenhas, MD: Fantastic. Unfortunately, this program is coming close to an end, so I’ll ask Srdan. From everything that we’ve talked about, we’ve covered a lot of stuff. Any last clinical pearl you want to provide the audience in terms of the different types of patients, cytopenic MF [myelofibrosis] patients? Do you have anything to end with?

Srdan Verstovsek, MD, PhD: There is no 1 patient profile that fits all and I think Aaron elaborated very well on that. We need to individualize not only in prognostication but also in the therapeutic approach. I think that through our experience together, we are cognizant of the cytopenic vs proliferative nature of some patients. They are really on a spectrum here but for practical purposes and perhaps for therapeutic purposes, we can start talking more about cytopenic vs proliferative. Because cytopenic cannot be treated very well with what we have right now, with ruxolitinib and fedratinib, but not having a platelet drug or an anemia drug then it helps. I think that is a practical and useful discussion and I hope with the new medications including momelotinib, pacritinib, and even the new combinations we will be able to dissect who benefits the most from these different therapeutic approaches. And we’ll have the algorithms that will not be straightforward all-inclusive therapies for everybody but we’ll have an array of possibilities.

John Mascarenhas, MD: Great. I think the other aspect is that hopefully we’ll get to a paradigm where we can figure out how best to cycle or incorporate these drugs one after the other because it could be different for different patients.

Transcript edited for clarity.