Exploring Myeloproliferative Neoplasms with Ruben Mesa, MD: What's on the Horizon?

At the American Society of Clinical Oncology (ASCO) 2018 annual meeting in Chicago, Rare Disease Report^® sat down with Ruben Mesa, MD, director of Mays Cancer Center, the newly named center home to UT Health San Antonio MD Anderson Cancer Center, to discuss myeloproliferative neoplasms and other rare cancers.

Rare Disease Report^® (RDR^®): As an expert in myeloproliferative neoplasms (MPNs), can you speak to your experience with MPNs and what your approach has been with these rare diseases?

Mesa: The matter of myeloproliferative neoplasms, as I tell my patients, [is they] are not rare or common cancers. What I share with folks in the era of precision medicine and precision oncology [is that] we find, to some degree, all patients have a rare disease. [That’s] because however their disease affects them, whether it’s something that you don’t hear much about, like myelofibrosis or polycythemia or even if it’s something [common] like breast cancer, there’s probably a thousand different subtypes, each one of which is kind of rare in and of itself.

My approach with these diseases really focuses on trying to individualize the therapy as best we can. That begins with the genetic understanding of the disease, which we learn more about every day, but [it also includes] trying to really understand and mirror that with how the disease is affecting them, what symptoms [it gives] them, what difficulties [it] has given them, and then being mindful of their overall health, their fitness, as well as the rest of their life circumstances. The same disease can occur in someone of 30 or 80 years of age, but how we approach it really needs to be quite different.

RDR^®: What are the greatest challenges in treating MPNs?

In myeloproliferative neoplasms, there are several challenges. One [challenge is having an] early understanding of why the disease develops and why it progresses. In many ways, [MPNs] are similar to other diseases. I’d say we’ve learned more about the genetic pieces, but it’s not fully mapped out. What I share with patients [is that] it’s a bit like a jigsaw puzzle that has 500 pieces, but we only have 200 on the board. We understand some parts—there are some parts of the picture that are fleshed out—but they’re not all there.

It’s before we have all those pieces [we ask], ‘How do we make the best decisions for patients that need decisions made today?’ There is some guess work involved; there is some use in experience; and there is trying to pull information [in] a collaborative way, a team-based way around the world as best we can so we can fill in those other pieces as quickly as we can.

RDR^®: Would you say you’re an advocate for the team approach in rare diseases like MPNs?

Without question, I think teamwork is crucial, and I think there [are] different layers in terms of a team. [First of all,] there’s a team in terms of caring for the patient. When you have a rare disease—and there’s rare diseases that may be hematologic, such as MPNs or others—needing a broad team is important. Typically, there are things that need multiple specialists, so that might mean multiple physicians working together with the entire care team (nurses, practice practitioners, and others, whatever their role is in helping to manage that disease). Clearly, there’s sometimes a caregiver that’s a key part of that team in terms of how they help best support you and help the team support your efforts.

There’s an educational need. When you have a rare disease, the difficulty is getting good information and understanding what it really means because rare diseases don’t tend to be diseases that are in the social discussion.

If I have a patient that has breast cancer, they’re able to relate to it based on the experience of their sister, their mother, or a friend. If I tell someone that they have amyloidosis, they ask, ‘What is that?’ There’s no easy frame of reference. Having good information is crucial and having information that patients can have physicians and their team link back to them that is accurate for them is also important. There’s a lot of information out there but finding information that’s accurate not only for a patient’s disease and where they stand with their disease is really important.

RDR^®: Are there any programs you have worked on with other institutions to approach MPNs or other rare cancers?

MPNs are about teamwork; I collaborate with Ron Hoffman who leads our MPN research consortium, [the] National Cancer Institute related consortium of over 10 centers, including mine at UT Health San Antonio, that look at new therapies for patients with difficult myeloproliferative neoplasms that is one of the most organized of those groups. It’s great collaborations with the patient community, ranging from the MPN Research Foundation, to the MPN Education Foundation, to many others that not only provide educational information for patients, but really collaborate.

There’s the Leukemia and Lymphoma Society, which truly tries to help these individuals out in a range of ways, both in terms of funding research as well as being given a range of other options. My prior institution of the Mayo Clinic, my current institution of Mays Cancer Center, Memorial Sloan Kettering, and Mount Sinai amongst many others are deeply dedicated to these groups of diseases.

RDR^®: What do you think other physicians should keep in mind when treating MPNs and other rare cancers?

I think the key both in MPNs and other rare cancers in the eyes of the treating hematologists or medical oncologists, is that frequently the endpoints of care and the art of care is different. They are diseases that behave very differently than a lymphoma, an acute leukemia, or a colon cancer. In each of these diseases, I think it’s really [about] learning what to expect from each of the diseases, modifying your expectations, and really knowing what those endpoints of care are.

I know that frequently patients with MPNs may both look, and appropriately seem, perhaps less ill to their treating physicians than the people they saw before or after. I always encourage physicians to really look at each patient individually. If you have a patient with polycythemia vera (PV) and the patient you saw previously had pancreatic cancer, the patient you see afterwards has an advanced brain cancer, these are very sick individuals, and yes, the person with PV looks very healthy in comparison. The comparison doesn’t really matter at all though because these are 3 very different individuals in very different circumstances. Being mindful of the needs of that polycythemia vera patient is important, even if he or she sometimes appears to be the healthy person you see that day.

Rare disease patients can look fine, which makes rare diseases so difficult. Rare disease patients are just really different from the other patients a physician sees. Physicians see someone with an advanced ovarian cancer with a feeding tube after their polycythemia vera patient, and the polycythemia vera patient looks fine, but that doesn’t mean he or she is fine.

RDR^®: What are the most exciting innovations on the horizon for rare diseases like MPNs and other rare cancers?

Without question, the exciting theme about treating difficult disease like cancers pertains to trying to make the treatments more precise, which involves the genetics of the cancer. Increasingly, we’re learning that there are many layers to genetics that go back beyond DNA. It’s about individualizing therapy; that’s one key angle.

The second innovation is the power of the immune system, and I think we’re only starting to tap into that to some degree. There has been great activity to help revolutionize much of the care in cancer by stimulating the immune system. Still, at a rudimentary level, that’s still very non-specific. The next generations are about how we stimulate the immune system as well as how we deliver either cellular-based therapies that are engineered for specific cancers.

What are called the CAR-T type therapies, they’re a bit like the first iteration, if you think about the old TVs, they were black and white and cost a ridiculous amount of money. These treatments have evolved and are evolving where soon there will be hi-def plasma screen therapies. Again, the early ones are both expensive and have a lot of side effects as we evolve, but they will probably be transformational.