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John O. Mascarenhas, MD, and Kapila Viges discuss how MPN care is being transformed by aligning research with patient-centered outcomes.

Physician’s Weekly (PW) met with John O. Mascarenhas, MD, and Kapila Viges to learn how the latest research impacts care for patients with myeloproliferative neoplasms (MPN).

PW: What do you see as the most beneficial of all the combinations that are being explored right now?

Ms. Viges: It’s important to remember that options matter for patients. In myelofibrosis and MPN, more broadly, these chronic diseases, patients live for decades in relatively stable health. But knowing that there are options over time if something either stops working or their disease progresses, knowing that they can sequence through a few more options and maybe even some newer combinations that are interesting, brings a lot of hope and promise for patients and gives them some comfort as they navigate their journey through their disease.

Dr. Mascarenhas: The key to treating myelofibrosis is that you need options to tailor the therapy. It’s not one treatment fits all. So, whether it’s a monotherapy, a combination, or when to switch, each agent to pick is individualized for the patient. The more options we have as physicians, the more likely we can tailor and optimize a treatment for an individual.

Ms. Viges: That’s our motto—options matter. We at MPN Research Foundation recently surveyed 676 patients to learn their treatment goals. Of these, 50% said improved quality of life. More specifically, 40% said relief from symptoms is their primary goal. Patients value the options coming online, the combinations, and how we measure and manage symptoms.

Dr. Mascarenhas: Symptoms are complex and sometimes hard to measure. It’s hard to measure the actual or absolute benefit of a given therapy or combinations with symptoms. So, it’s been an area in our field for drug development where we’re trying to figure out the best way to capture that benefit for any individual patient because some patients may benefit to greater degrees than others, and not all therapies are ideal for any given patient. It is a complex world that we’re living in in terms of trying to navigate this. But, patients are symptomatic, and they want to feel better. Physicians want to make patients feel better, but we also want to extend survival with good symptomatology. So it’s a mixed picture. For some patients, the symptoms may be systemic or cytokine symptoms.

Do you think trials will continue considering additional endpoints or exploring more markers?

Dr. Mascarenhas: One of the fundamental deficiencies in our field is that we currently measure spleen and symptom reduction as our primary endpoints for clinical trials because we started the field with JAK inhibitors. They don’t do it for everyone perfectly and don’t always maintain it indefinitely for every patient. So that’s some of the nuances, but we are moving into an area where we’re looking now at therapeutics that might be able to change the natural disease history. The problem with the trials we design often is that we don’t follow patients because you need a lot of patients; you need a lot of power to do it.

Statistically, we don’t always follow them to the point where we can confirm survival. So we are in a desperate search for surrogate markers that you can look at earlier on, whether it’s spleen reduction or symptom burden even, or bone marrow fibrosis reduction, driver mutation reduction, cytokine reductions, things that you can measure maybe at a six month period that may correlate and associate down the line with a survival benefit. It’s key for us as investigators and the research foundation to figure out how we do that as a group so that we’re not at the stumbling block where we’re trying to understand what we are achieving.

Is there a concern in academic research about forgetting the patient and their preferred outcomes?

Ms. Viges: We completed a survey with our patient caregiver community with 676 responses. More than 70% of patients said their goal was understanding progression. How do I slowly stop, reverse, or, as you’re saying, ultimately modify the disease so that I don’t progress? It’s important to recognize that patient treatment goals need to be heard and surfaced. That’s where our role of bringing together the patient, the research community, and the industry sponsors to align goals for treatments brings meaningful benefits to patients that we can measure through the endpoints. And so coming back to that point of looking at it through a much more broad lens of what matters to patients and bringing that voice into the research and development life cycle as early as we can so that our programs are progressing in a way that at the end of the day when these therapies become available, we are measuring things and impacting patients in the way that are meaningful to them.