<p>Extensive patient education and shared decision making are critical for the successful treatment of myelofibrosis. Current treatments primarily alleviate symptoms such as spleen-related issues without significantly altering disease biology. However, our featured experts are optimistic about emerging targeted therapies that may improve durability and potentially slow the progression of myelofibrosis.</p>

Most people have heard of lung or breast cancer, but explaining to a patient that they have myelofibrosis can be challenging. Sometimes they feel well, so it is difficult for them to comprehend that they may need treatment with medication or a transplant.

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We do not have a large “menu” of curative treatments to offer to patients with myelofibrosis, so I think where the physician can be helpful is with patient education (eg, helping them understand what a treatment can and cannot do for them). Providing enough education so that the patient knows when to call their physician but also when to wait is a balance. Some patients struggle with the potential for progression. Thankfully, progression happens rarely, and it happens slowly. So, you and the patient can plan (ie, start getting ready for a therapy change, transplant, or clinical trial).

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When treating a patient with myelofibrosis, I consider who the person is, where they live, what their health literacy is, and what resources are available to them. All these things should be taken into consideration from the very beginning. Luckily, many therapies for myelofibrosis are oral and do not require a specialized center to administer. Virtual care can really help to increase access for many patients.

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Currently available treatments primarily improve spleen volume and symptoms but do not meaningfully alter the disease biology of myelofibrosis. For me, it has been exciting to see second-generation medications become available for myelofibrosis. For example, we have a number of targeted agents (ie, mAbs, bsAbs, and ADCs) in development for CALR-mutant myelofibrosis that seem promising.

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Finally, with JAK2-mutant myelofibrosis, the question has been whether we need to block something in addition to JAK2 because the JAK inhibitors we have do not modify the disease. I think the more selective JAK2 inhibitors that are currently in the pipeline are really exciting.

As Dr Hobbs mentioned, myelofibrosis is such a rare disease that it is hard for people to comprehend its potential consequences. It is important to educate patients about expectations. On the one hand, we want patients with myelofibrosis to know what to look for; however, raising the idea of every single thing that could possibly happen can cause a lot of anxiety. So, it is important to ease anxiety, set up the right expectations, and start the discussions if things are moving early on so that patients are not surprised. Usually, if we keep following a patient with myelofibrosis, we develop a sense of whether they are about to progress, where the medication is working, and where we should be more cautious.

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Support networks are also important, especially in areas where we do not have many centers. For younger patients with myelofibrosis, I think that social media can be particularly beneficial. It can help raise awareness and make patients feel heard, and we can even utilize similar patient stories to help inform the next steps when treatment decisions become difficult. Overall, I think that patients can be the best advocates.

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I also think it is exciting that we are entering a targeted era for myelofibrosis (eg, with the novel JAK inhibitors). The combination therapy results have been a bit rocky. The purpose of combination therapy is not only to enhance or synergize the established end points and deepen responses but also to make responses more durable. I think that it is important to show long-term benefit in these studies to understand whether we can treat with more than 1 drug long-term. The big question is: Are we actually improving the disease (ie, prohibiting progression)? That is what we all want to see.

Like Dr Masarova alluded to, patients with myelofibrosis often come in already somewhat educated about the different treatment options or experiences that others have had. I think that this is a patient population that tends to seek out information and comes in with some baseline knowledge.

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There are some patients with myelofibrosis who present with a clear phenotype that would respond to a specific therapy, but more often you will have patients with symptoms that could be addressed in a number of ways. I think that when you spend the time with patients, especially during the initial visits, it pays dividends down the road. When patients receive comprehensive information up front, they can then come back in the future with better questions and understanding. For me, treatment decisions are shared decisions; I mention the 3 or 4 different treatment approaches that are reasonable, and together we figure out what we are going forward with.

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When you start any kind of treatment, it is important to set expectations. For example, for patients who have really bad night sweats or itching, make it clear to them that the goal of a particular treatment is to improve those symptoms. Then, if those symptoms do not get better or if new symptoms develop, patients know that they should contact us.

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Currently, there is a push to have more targeted approaches that target driver mutations. At the upcoming 67th American Society of Hematology (ASH) Annual Meeting and Exposition, I think that we will see data on novel ways to target CALR, including ADCs, as well as JAK2-specific approaches. I do not think that these are going to be the complete answer to myelofibrosis, but I do believe that they may form a new backbone as we establish better strategies for combination therapies.

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We are also going to get updated long-term data from some potential combination strategies at this year’s ASH meeting, for example, the long-term follow-up of pelabresib in combination with ruxolitinib from the MANIFEST-2 study. If we are thinking about the role of combination therapy, we should be very interested in these long-term outcomes. And I do applaud the fact that MANIFEST-2 kept people on trial so that we can start to answer these questions.