Bone Marrow Transplant for Patients With MF


Expert panelists review important disease-related and patient-related factors when considering bone marrow transplant in patients with primary myelofibrosis.

Ruben Mesa, MD, FACP: Before we pivot to talk about new therapies—of which there are many—let’s circle back to what our gold standard of backup options has been, which is allotransplant. My thoughts on transplants have evolved during my career, particularly in the era of our new therapies. Transplant, to be successful, needs to avoid being a salvage therapy for a patient in extremes. You can do it, but the likelihood of success is low. I think about all the patients I’ve had who had transplants, and for whom I was really pleased with their outcomes. It was all people who had a transplant a little before we needed to do the transplant. If you need to do the transplant because they have a big spleen, they failed 5 therapies, they have lost 30 pounds in weight, their blasts are at 12%—none of those patients does very well. Let’s just be honest. They do better; they clearly do better when they’re in their peak of response. It means it’s the time they want to do the transplant the least, but that has been my impression. What do you think, Jamile? Where does transplant fit in? What’s that discussion you’re having with the reluctant 65 year old?

Jamile Shammo, MD, FASCP, FACP: I totally agree with you, Ruben. It’s so true that the outcomes are always better with patients who either had a lower risk with ENT1, or those who have ENT1 high-risk disease who are in the prime of their response to JAK inhibitors when they don’t want to do this. There is only curative treatment for myelofibrosis, but the clinical trial data don’t lie, right? There was this abstract from ASCO [American Society of Clinical Oncology Annual Meeting] that looked at a massive number of myelofibrosis patients—over 8000. It’s a meta-analysis, essentially.

Of course, I understand meta-analysis and the problems, but it’s also a huge number of patients. They looked at the outcome of patients who’ve undergone this treatment, and it showed—which we all already know—that you can salvage up to 50% of the patients. The problem is that you’ll lose 30% of those patients to nonrelapse mortality. That’s the problem that I have with people who have things like diseases with high ENT1 risk. You have someone who may have a terrible MIPS [Mutation-Enhanced International Prognostic Scoring System] score, but with high-risk ENT1 diseases, you’re going to be faced with a 30% chance of nonrelapse mortality, or you’re going to tell them again, as this analysis suggests, that “You have a 25% chance of having severe graft-vs-host disease [GVHD].” That’s something that they’re going to be dealing with. It’s difficult; I can tell you from practical experience. I’ve sent multiple patients to transplant, and they all came back to me saying, “Thank you, but no thanks.” I can only give people options, but I couldn’t agree with you more that the concept of a cure isn’t something you can simply brush off, especially when you don’t have a curative treatment otherwise.

Ruben Mesa, MD, FACP: It’s very true. Srdan, what would you suggest to folks watching this, in terms of the management of ruxolitinib or fedratinib pretransplant? Let’s say someone is going to have a transplant. What’s the role of medical therapy beforehand? Do you keep it going all the way to the time of transplant? Do you do a taper? Do you extend it beyond day 0? As we speak, I have 1 of my patients being transplanted at your wonderful center [The University of Texas MD Anderson Cancer Center] who is on day 0. These are real-world scenarios.

Srdan Verstovsek, MD, PhD: The JAK inhibitors are supposed to be given to our patients, in our experience, until the day before the transplant procedure happens, in terms of giving patients pretransplant chemotherapy. We don’t want to have any major gap between the stopping of the JAK inhibitors and starting the transplant-related chemotherapy because of the possibility of a rebound in symptoms. That’s a very well-known complication from stopping therapy for patients who are responding. As Jamile said, patients go into the transplant when they’re responding. If you stop the therapy 1 week before, then they’ll get in trouble, most likely within that week. You can give it only so much time before you give the chemotherapy for the transplant. We’re also looking at the continuation of JAK inhibitors into the transplant procedure for 10 to 14 days. We hope to see whether this will have any influence on the outcome. Preliminary results published by our European colleagues said that it’s very feasible, and it should be done. It perhaps doesn’t have a main role yet in every practice because we’re very cautious about it. The standard practice would be just stopping the day before chemotherapy, but we’re open to these suggestions.

Even if you do have a patient whom you see for a transplant for management of myelofibrosis, and there’s a donor already for the transplant, that doesn’t preclude us from treating that patient with the JAK inhibitors. That must be clearly stated, right? The transplant and JAK inhibitors aren’t exclusive of each other. Even when you have a donor, and it’s going be ready in a month or 2, why not utilize this month to optimize the care of the patients by giving them a good dose of JAK inhibitors, or even transfusions? It’s not going to harm anyone to get that quality of life, to get that spleen as small as possible and controlled well. That way, the optimal care at transplant is strong. One application—a pill to a transplant—and that continuation of the benefits will make the patient’s outcome the best.

Ruben Mesa, MD, FACP: Very true. It’s amazing to see how this has evolved. Indeed, we’ve even seen that JAK inhibition has value pretransplant and in somewhat of an NPN-independent fashion. We’ve seen that ruxolitinib has an indication for GVHD, where there are anti-inflammatory properties. Certainly, there are ongoing studies questioning whether JAK inhibition should continue during the time of transplant, or at some point afterward. The trials are important because there clearly can be challenges in terms of thrombocytopenia and other things for patients to face.

Transcript Edited for Clarity

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