Ritchie Reflects on Research Underway in Myeloproliferative Neoplasms

Ellen K. Ritchie, MD

Investigators are in the midst of exploring novel therapeutic regimens for patients with myeloproliferative neoplasms (MPNs), as well as working to obtain a deeper understanding of the biology of these rare conditions.

With the FDA-approved agents available for these rare malignancies, such as interferon and ruxolitinib (Jakafi), researchers are now looking to combine these therapies with other biologic agents to improve response rates and quality of life (QOL).

Moreover, innovative single agents are being explored, including SL-401—a targeted therapy directed to the interleukin-3 receptor CD-123—which is being tested in a phase I/II trial for patients with advanced, high-risk MPNs, including systemic mastocytosis, advanced symptomatic hypereosinoophic disorder, myelofibrosis, and chronic myelomonocytic leukemia (NCT02268253).

“MPNs are rare diseases and we have a lot to learn about these diseases and, as a community oncologist, you might not see many of these diseases in a lifetime,” said Ellen K. Ritchie, MD.

OncLive^®: Can you provide an overview of your presentation on MPNs?

Ritchie gave a lecture on the landscape of MPNs at the 2017 OncLive^® State of the Science Summit on Hematologic Malignancies. In an interview during the meeting, she highlighted the collaborations at Weill Cornell Medicine/NewYork-Presbyterian Hospital with MPN research, current and emerging novel treatments, and the possibility of using immunotherapy to treat these patients.Ritchie: This talk was to introduce this audience to our program at Weill Cornell Medicine. Dr Richard T. Silver—who has been at Weill Cornell Medicine forever—really piloted the use of interferon in patients with myeloproliferative diseases and we are trying to expand. We are an institution that has the longest experience in treating patients who have MPNs with interferon.

We were really excited to move into some of the newer longer-acting interferons, and combining interferon with other agents to treat [patients with] myeloproliferative diseases. We are also looking at new ways to support patients with myeloproliferative disease, including programs looking at the association of pulmonary hypertension in patients who have MPNs, as well as collaborating with our other departments at Weill Cornell Medicine—such as cardiology—to come up with better ways to recognize this problem and treat this problem in patients.

Young patients actually get these diseases [too] and we have patients on medications that affect their fertility, so I am working with our Department of Urology looking at male infertility in particular and how we can allow young patients with these diseases to have families, go forward, and not interrupt their treatment too much. That is another exciting area that we are delving into.

With our gastrointestinal (GI) group, we are looking at a connection between patients with inflammatory bowel diseases and myeloproliferative disorders, and we are excited doing exploratory work in this particular area. We are interested in looking at new drugs to treat these diseases; our leukemia group is really exploring the use of immunotherapy in treatment of patients with acute myeloid leukemia. We are hoping to piggyback on that and look at some of these immunotherapies in myeloproliferative diseases, as well.

Are there any known risk factors for MPNs?

Ruxolitinib (Jakafi) is FDA approved for the treatment of patients with polycythemia vera and myelofibrosis. Can you speak to the impact this agent has had thus far?

We are very lucky that we are in a major medical center in Manhattan, so for a disease that affects many different organs and organ systems, we have excellent teams of cardiology, urology, GI, and leukemia experts to collaborate with to help these patients through all phases of disease and support them. No, it is really hard to say. There probably are genetic risk factors. That is something that, as we learn more about the different genes—which are involved in myeloid diseases and we start to look at families—we are going to see more of these genetic risk factors for these diseases. Certainly, modern life exposes us to a lot of things, and what the relationship of these exposures are to the development of cancer [is something that] we still are sorting out. It was very exciting when JAK2 was discovered as being a genetic target in myeloproliferative diseases. We really hoped for a second [that it would be like] imatinib (Gleevec)—some sort of medication that we could use to target JAK2 that would really shut these diseases down, make symptoms go away, and make people lead more normal lives.

While ruxolitinib has been an important drug and has improved quality of life (QOL) for a lot of patients with MPNs, it is not a home run like imatinib was. It doesn’t really make all of the symptoms disappear or the disease go away.

Is there any hope for immunotherapy in this disease?

We are looking at how to exploit these pathways using other drugs, potentially combine ruxolitinib with other drugs to improve its efficacy, and maybe getting ourselves closer to that home run would be a real goal in the next few years. [These studies] are really early. We have a trial at Weill Cornell Medicine using SL-401, which is an antibody to the CD-123. We are looking at that in patients who have myeloproliferative disorders—mainly myelofibrosis, and looking at patients who have chronic myelomonocytic disease, which is sort of its own category of a combination of MDS and a myeloproliferative disease. We are early on in treatment; it looks like there are some early responses. It will be interesting to watch how durable those might be, or how these are going to develop over time. Hopefully, it is something we can add to our armamentarium to make the treatment of these diseases more robust.