What is the Role of Transplant in Managing Patients With Myelofibrosis?


Expert panelists consider the ongoing role of transplant for patients with myelofibrosis and discuss when it is more appropriate to explore systemic therapy options.


Naveen Pemmaraju, MD: I loved your summary, and speaking of disease modification, since you brought it up, the only curative modality, which we mentioned on this panel, is still the allogeneic transplant, and you are one of our world experts in that field. Dr Palmer, could you give us the overview on where things are with allogeneic transplant in myelofibrosis, anything new? What should we be looking for in 2023?

Jeanne M. Palmer, MD: With myelofibrosis and transplant, it remains the 1 curative option. There are a few things that have come out in the last year or two. First, there have been some nice data presented on using haploidentical donors, so half-match donors, which has always been a source of concern over engraftment issues, etc. Even though haploidentical donors are routinely used in multiple hematologic malignancies, in myelofibrosis it always brought pause when we were thinking about it. But there have been some very nice data showing that this is an acceptable donor. In fact, it’s probably better to use than a 9/10 mismatched unrelated donor, which is very nice. The big challenge with transplant is always, when do you transplant somebody? And this is something that is incredibly difficult to define. Which markers do you use? Which prognostic scoring system do you use? How do you talk to the patient about this in a way that they can make an informed decision? Because it’s not 100% clear.

There are certain patients where I said, “Yes, you absolutely need a transplant.” And there are some patients for whom I say, “You are totally not ready for a transplant yet.” But there are also a lot of patients in that gray zone, where you’re trying to convey very complex topics of what does this mutation mean? What does that mutation mean? What are our risk scoring systems? What are the caveats to those scoring systems that we use? And how do we use that to decide when taking part in a treatment plan that could cause them significant morbidity? And trying to find that right timeframe so we do it before they get so sick that we have bad outcomes as a result of it being too far advanced. That’s a hard one. How these many different new agents are going to fit into this transplant timing model is going to be another tough one. In all honesty, patients tell us what they want. If they know the information, they can articulate, “I want to move forward with this,” or “No, I’d like to try something different.” Hopefully, as these agents become more readily available, and as we have more experience with them, we will be able to look back and try to get a better idea of when patients should go to transplant. How do we put all the timing in this? Can any of these agents even be used in the post-transplant setting to help mitigate the risk of relapse? The opportunities are endless in terms of trying to understand this better, and it’s a great problem to have.

Ruben Mesa, MD: Let me build on something Jeanne said because I think it’s critical. I think that the decision to have a stem cell transplant in a disease like this is one of the most complex medical decisions a patient can make. The toxicity and mortality dwarfs that of most medical procedures. Compare it to open heart surgery, a valve, or other things, there are few things in the range of the mortality of transplant. There is a personal philosophical piece, in terms of, what does my life look like with serial medical therapy versus the trade-off of the front-loaded mortality of transplant, but the potential payoff of long-term survival? You might know how to answer that question with everything you have absorbed about the therapy, but for a patient, it’s really difficult. Then you start to factor in health literacy, potentially language and culture. It’s a lot to wrap your head around. Most patients, when they’re told they have myelofibrosis, have never known a person with myelofibrosis or have any frame of reference. If someone is told they have breast cancer, they have a frame of reference, good or bad, usually based on a family member or a friend who has gone through that process, and every piece of information in the lay media. The key piece from our end is recognizing that there is a knowledge gap regarding decision-making to get to that point that must be filled.

I encourage everyone, Jeanne and I both work in Arizona together, and I’ve had this relationship everywhere, this symbiotic relationship between the transplant and the nontransplant, as a bit of a check on each other. I shouldn’t put everyone on clinical trials automatically because the window for transplant may close because we’ve blown through, well, you’re on your fourth line of clinical trial. That’s probably well past the point that having done the transplant would have made sense. On the flip side, we aren’t doing transplant for patients in which the mortality isn’t appropriate. For a patient it takes a lot of time to digest all that information. There’s no way they walk in, need a transplant, and walk out saying, “Oh, that’s what I’m doing.” So again, encourage folks to think about it from that perspective. I would encourage you to refer possible transplant candidates, based on age or lack of comorbidities, as early in their treatment arc as possible, but really get acquainted with the transplanter. Don’t expect to come out of there and be listed for 6 weeks afterward. If you wait until the patient is in the hospital because they’ve got 20% blasts and someone wants to give them induction, that discussion should have occurred long ago.

Jeanne M. Palmer, MD: I want to echo that because, fortunately in my practice now, I see many patients who are transplant or nontransplant candidates, so I treat a lot of myeloproliferative diseases even in the absence of it, which is great because I form a nice long relationship with the patient. But when I do get consults, it’s much better to get them early because it’s not just the medical understanding and the decision-making process that goes behind it, but the resources needed to undergo a transplant, in terms of financial resources, caregiver resources, and time off of work, which can be up to a year. These are things that if you have that time, even years in advance, to start thinking about what that’s going to look like, that is an amazing benefit and a gift you can give to a patient. On one hand you might say, “Well, jeez, now they’re going to have this hanging over their head like a ticking time bomb,” on the opposite side of that coin, to have that time to be able to prepare for it in all the ways that need to be prepared is really important.

Ruben Mesa, MD: Not to dwell on this, but it’s a key part because it’s such a symbiotic piece. I once had a 31-year-old patient who was a patient of…who had ET [essential thrombocythemia], and they came with a very valid question. He’s said, “I’m 31. I want to get married. I want to have a normal life. I want to have a transplant so that I don’t have to worry about this disease.” And I realized, there wasno medical reason that this guy should have a transplant, but he was telling me [about a knowledge] gap. He traveled overseas because of the anxiety it was causing, and the way I tried to frame it, which I think is valid, is that being a transplant survivor is an illness. It’s a definable illness with its own mortality adverse effects and negatives. It is not, you wave a wand and now you’re back to normal health. I explained to him as I’ve explained to others, we could do it, but being a transplant survivor is a worse disease than having ET. I’m said, “This is not a trade-off you want to make because you’re going to be more ill because you had the transplant.” That made a big impact. People ask, why travel to see an expert? Sometimes we don’t change medicine, but if you change perception, you might sometimes have a significant impact.

Naveen Pemmaraju, MD: That’s the line right there. We talk about personalized targeted therapy, Ruben, in the clinic. That’s personalized targeted advice. That’s something we can carry forward in the new year.

Transcript edited for clarity.

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