Management of Low-Risk Primary Myelofibrosis

Harry P. Erba, MD, PhD: I want to come back and take us away from the brink of mortality and with advancing risk to circle back to the low-risk patient. We’ll talk about the Cervantes criteria. A very small percentage of patients, about 10% in that analysis, had low-risk disease. Krisstina, do you see these patients? Would you ever consider therapy for a low-risk patient, symptomatic or asymptomatic?

Krisstina Gowin, DO: Patients definitely present with low-risk myelofibrosis. In those patients, this is where we’re assessing whether they are associated with a symptom burden. In those patients who have low-risk disease by the DIPSS [dynamic international prognostic scoring system] or the MIPSS70 [mutation-enhanced international prognostic scoring system]—the more sophisticated prognostication tools—still have a significant symptom burden. Those are patients for whom we can consider intervening.

I recently worked with the CIBMTR [Center for International Blood and Marrow Transplant Research] and a group of academic centers looking at the role of stem cell transplantation. Interestingly, there was even a group within that analysis with low-risk disease who proceeded to stem cell transplantation. Some physicians would say that, for the treatment of myelofibrosis, the only true curative measure is allogeneic stem cell transplantation, and in patients who are wishing for a more aggressive and disease-modifying approach even in low-risk disease, some physicians are proceeding with that.

There’s not significant evidence to support that approach, and the best evidence is in the intermediate-2 and higher, and more recently considering intermediate-1a disease. We look at the patient’s goals, their risk status, and their symptom burden.

In general, though, for low-risk disease, we monitor these patients’ counts to see if they are transitioning to a higher-risk phenotype, a higher DIPSS. Are they having molecular evolution? Are there more high-risk mutations recurring over time? We’re taking all these pieces of the puzzle to decide when to initiate therapy and how aggressive to initiate therapy.

Harry P. Erba, MD, PhD: Thank you for that, Krisstina. You prompted a question I was going to ask you later because you are the 1 member of our panel who is a believer in stem cell transplant. You are a transplant physician, and I also think it’s because you’re probably the youngest, and it is a young person’s job to take care of these patients.

I’m going to come to a question for you: Our challenge in picking patients for the curative option of transplant is the data are intermediate-2 and high risk, but those are often the patients who are cachectic, have huge spleens, and have other issues that may preclude them from being an ideal transplant candidate. On the other hand, you have low-risk patients who may be healthy and able to undergo stem cell transplant, even with its risk.

My question for you is this: Is there anything you use in that low-risk patient to talk with them more aggressively about transplant, like mutation analysis or cytogenetics? Does that influence your opinion?

Krisstina Gowin, DO: Absolutely. That’s a great question. At the University of Arizona Cancer Center are using these molecular characteristics to help guide us. We know that there are particularly high-risk phenotypes within myelofibrosis, particularly the triple-negative patients, the CALR, JAK V617F, as well as ASXL1. These are extremely high-risk phenotypes: genotypes that can certainly have a higher risk of transformation to acute myeloid leukemia down the line.

The idea of intervening when patients are a bit younger, a bit more robust with higher performance status, fewer comorbidities, less splenomegaly, and fewer cytopenias is certainly attractive for a conversation with the patient. There are certain approaches, so for patients who are developing more splenomegaly, we can certainly use ruxolitinib as a bridge to control the splenomegaly symptoms before we take them to allogeneic stem cell transplant.

This is such an institutional approach, so every institution and every academic center for transplant will have a different approach and a different discussion. As a community, we’re moving toward an earlier discussion. For community physicians, I would like to impart the importance of early academic referral.

Often, we see that these patients are referred to academic centers when they’re already symptomatic from their disease. They have intermediate-2 or high-risk disease, and they’re saying, “Now it’s time to transplant.” No. It could have been a lot smoother. The donor selection takes time. All these things take time, so if it’s early within the disease course it can be better for the patient.

Harry P. Erba, MD, PhD: I agree. I’m going to remind our viewers that you opened the transplant door, so I’m jumping ahead in our agenda, and I’m going to keep you on the spot as our local expert. Let’s say you have a myelofibrosis patient. I’ve heard that if you don’t do a myeloablative preparative regimen, you might as well not do it in a patient with myelofibrosis. It’s not going to work. Any truth to that? How do you select the regimen?

Krisstina Gowin, DO: I’d like to clarify, I’m not an allogeneic stem cell transplanter.

Harry P. Erba, MD, PhD: Close enough, close enough.

Krisstina Gowin, DO: I have done some research in this area. In general, this is a polarizing issue within the transplant community, and there are not significant data that would sway one to myeloablative versus reduced intensity conditioning.

This is an institutional preference. This needs to be looked at in the literature. It’s a challenge because myelofibrosis is a rare disease, and to do prospective analysis in this is very difficult. I don’t know if we’ll ever achieve that, so continued retrospective analysis will help move the ball forward. To answer your question: It’s polarizing, and it’s controversial.

Transcript Edited for Clarity

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