Case 2: Considerations for Optimizing Therapy in High Risk MF


Ruben Mesa, MD, and panel discuss considerations for optimizing therapy in high risk myelofibrosis.

Ruben Mesa, MD: What are your triggers for initiating therapy in myelofibrosis [MF]?

Jamile M. Shammo, MD: That’s a good question. When you talk about anemia, at least there’s a little bit of objective measure if you have someone whose hemoglobin may become less than 10 g/dL. Maybe they’re heading toward transfusion dependency. That’s a little easier. You don’t want it to become transfusion dependent. If they are, you want to reverse that, although that becomes a little harder. When it comes to symptoms, that’s difficult. I have seen patients who have decent-sized and large spleens who have no symptoms, which is mind-boggling to me. I don’t understand how that happens. A lot of times, it may be that they changed their level of physical activity so that they could minimize their symptomatology. Be that as it may, what I do truly mirrors what I see with the NCCN [National Comprehensive Cancer Network] Guidelines. It’s typically either splenomegaly-related directed treatment or anemia-related directed management. That’s how I typically start treating my patients. You’re going to like this, Ruben. At baseline or even at the time of diagnosis, I will usually do my MPN10 [myeloproliferative neoplasm] Symptom Assessment Form. At the beginning, it may not be, but I will keep doing this until we understand the score. If that is truly getting worse, we might initiate treatment accordingly. It’s strictly by number when it comes to anemia or by symptoms if driven by splenomegaly.

Ruben Mesa, MD: Wonderful. Stephen, what are some of the risks associated with undertreatment of myelofibrosis?

Stephen Oh, MD, PhD: I would just start by echoing what Jamile said. It is somewhat surprising that patients’ perception of symptoms varies. Some have mild splenomegaly and are quite symptomatic from it. Others have what we would consider a pretty decent-sized spleen, and they don’t seem to be having symptoms. In my experience, 1 theme is that they grow accustomed to dealing with some of these issues, and if you do start them on treatment, they often say, “You know what? I realize I wasn’t actually feeling OK because now I feel better.” That gets to your question, Ruben: What are the dangers of undertreatment? It’s that these patients are actually suffering to some extent with symptoms that could be addressed earlier, but for some of the reasons we just outlined, they’re delaying the initiation of therapies that could help.

Other potential issues can occur. If there is that survival extension with extended treatment with ruxolitinib, when you delay treatments, you’re delaying or depriving that potential benefit. Second, if you want to extrapolate, you could argue, not without specific data, that earlier initiation of treatment could be even more beneficial. That’s speculative, but there is that possibility that delaying treatment is leaving patients at risk of not receiving that kind of benefit.

Ruben Mesa, MD: Prithviraj, regarding the case that was presented, how does the spleen, symptoms, and age factor into your decision-making in terms of treating this patient? Your group presented some really intriguing data from the [The University of Texas] MD Anderson [Cancer Center], suggesting that over the last decade, survival in MF is longer and that is probably at least in part tied to exposure of ruxolitinib. Weaving that all together, how does that relate to this patient?

Prithviraj Bose, MD: Ruben, there are 2 slightly different paths you have to go down when you’re evaluating a patient with MF. The first is to assign risk, and you can use any of these models. I agree with Steve. I tend to use the MIPSS70+ [Mutation-Enhanced International Prognostic Scoring System] version 2.0. Thankfully, these are all on the web, and you can just punch the numbers in. That is to determine if they need transplant. Once that is done, we move into the sphere of what their clinical need is. As Jamile said, there’s a fairly clear demarcation between whether they need a JAK inhibitor or if they need anemia-directed therapy, while recognizing that there are patients who need both. The survival benefit of ruxolitinib is something that has been shown in the long-term analyses of the COMFORT trials. That is something important to consider. As Steve was saying, there is something to be said for earlier treatment. I always keep all those things in mind, but I try to look for a clinical indication for a JAK inhibitor. If that is there, I will definitely go with that, considering the improved survival.

This transcript has been edited for clarity.

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