Individualizing Treatment Approaches in MPN - Episode 12

The Role of Transplant in Myelofibrosis

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Experts discuss the role of transplant and evaluating options in patients with myelofibrosis. 

Ruben A. Mesa, MD: The first decision for your patients with myelofibrosis—after you have a good sense of the disease burden and their prognosis—is whether you pursue observation, stem cell transplant, or medical therapy.

Observation is for a very select few who are low-risk asymptomatic, almost incidental. There are times it’s appropriate. Someone has been found to have incidental splenomegaly. Medical therapy is something we’ve discussed at length for the data with ruxolitinib. Stem cell transplant is a complex decision, but it begins with the higher the risk of prognosis, the better the candidate for transplant. Other clear factors are the patient’s aggressiveness and personal views on pursuing stem cell transplantation.

When an individual is going to undergo transplant, transplant can be beneficial and clearly can cure myelofibrosis with the risk of outcome being affected by a range of things. Indeed, there’s even prognostic markers for trying to predict outcomes for myelofibrosis. We’ve indeed found first that stem cell transplant is probably the most beneficial if the disease is not overly advanced. Individuals who have already progressed to acute leukemia, who have multiple adverse-risk factors in terms of organ function, or who have high-risk molecular features, all those are indicators of probably not having a successful course with stem cell transplantation.

We do know that as it relates to medical therapy, patients are diagnosed. If they’re higher risk, it’s not a question of transplant or JAK inhibitor. It’s more likely they begin on a JAK inhibitor. If they have improvement in their status, a shrinkage of their spleen, then we pursue the transplant. 

Early on, there was a challenge that individuals sometimes might feel much better and mistakenly feel that they might be able to forgo transplantation because they’re feeling better. We’ve found that probably that’s the optimal time for them to pursue the transplant, to undergo the transplant when they’re at their optimal response.

People have asked the question, should we continue JAK inhibition during the time of conditioning or post-transplantation? Both of these are open questions. Ruxolitinib has been approved as a therapy for graft-vs-host disease [GVHD], so it does have a benefit and there are different approaches being explored. Keeping it going during the time of transplant at a lower dose to decrease the risk of GVHD also might have a favorable impact, decreasing the risk of relapse from the disease. That is also being looked at for individuals who have higher-risk molecular features or have other reasons to have a higher-risk transplant.

We are continuing to learn more as we evolve, but undoubtedly JAK inhibition and transplant play an important role of interpolating pretransplantation possibly during and after the transplant.

Additionally, we have learned that the dosing in the peri-transplant period is important. It is probably wise not to try to abruptly stop ruxolitinib in that conditioning regimen period. If they’re on higher dose, let’s say 20 mg twice a day, if it is going to be discontinued, tapering them down to a more modest dose is probably beneficial. So is keeping that therapy going until the conditioning has begun, so the conditioning itself helps blunt any cytokine spike or other difficulties an individual has with the discontinuation of the ruxolitinib.

Without question, JAK inhibition has been a benefit in the overall transplant process. Undoubtedly, we will learn more about how to optimize that intersection between those therapies and perhaps some of the other therapies that we have looked at and have been discussing.

Pankit Vachhani, MD: It’s great that we are talking about transplant for myelofibrosis. We should remember that that is the only modality that is a potential cure for myelofibrosis. We restrict allogeneic stem cell transplant consideration to those who were less than 70 years of age, with some rare exceptions of course. Those who have DIPSS [Dynamic International Prognostic Scoring System] intermediate 2, or high-risk myelofibrosis, are advised and recommended to proceed to stem cell transplant. DIPSS low-risk patients, or intermediate 1, are not referred for a stem cell transplant at the front. 

If there are signs of progression—for example, if they have leukocytosis, worsening of anemia, addition of new symptoms, or loss of spleen-related response, or if there is evidence of more peripheral blood blast or bone marrow progression—then those patients are referred for stem cell transplant for myelofibrosis. When we do that we definitely taper off the JAK inhibitor, usually ruxolitinib at the point where the conditioning regimen begins. In the post-transplant setting, we do not use ruxolitinib at present. That is because of evidence for the use of ruxolitinib as maintenance therapy after allergenic stem cell transplant for myelofibrosis. The concerns related to myelosuppression or delayed engraftment are also things to consider.

Transcript edited for clarity.