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Expert Discusses Latest Developments in MPNs

Jonathan Alicea and Gina Columbus
Published: Wednesday, Jul 26, 2017

Dr. Rami S. Komrokji
Rami S. Komrokji, MD
Diagnostic and treatment advances have advanced the field of myeloproliferative neoplasms (MPNs) over the past several years, says Rami Komrokji, MD, who discussed MPNs at the 2017 OncLive® State of the Science Summit™.

Komrokji notes, however, that further refinement is needed with molecular testing, risk stratification, and the development of novel therapies.

In an interview with OncLive, Komrokji, vice chair of malignant hematology and section head for leukemia and MDS at Moffitt Cancer Center, shared his insight on the various types of MPNs, how these diseases can be diagnosed and managed, and the next steps needed to improve patient outcomes.

OncLive: Please provide an overview of your talk on MPNs.

Komrokji: The field had evolved in the last few years with all of the discoveries in biology, the integration of somatic gene mutations in diagnosis, and risk certification for those patients. I gave a bit of an overview of the biology of the disease, the difference between the disease initiating, and mutations versus the phenotype driving mutations. I went into a little bit more detail about those mutations like JAK2 V617F, the calreticulan mutation, or MPL mutations— what we call phenotype-driving mutations.

We also discussed the risk models used for every disease—how we risk-stratify the patient—and we briefly went through an algorithm of how we managed those patients. In PV, we discussed the need for phlebotomies and cytoreduction therapy in patients who are considered high risk. We discussed how to manage patients with myelofibrosis based on the risk. If they have a higher risk, we consider them for transplant. If patients have constitutional systems, JAK2 inhibitors are becoming the standard of care for them. If they are predominately cytopenic or anemic, then there are different options, including immunomodulatory agents. 

Finally, I tried to update on what was presented at past ASH Annual Meetings. There are a couple of trials looking at newer formations of interferon, which had been a treatment commonly used in MPNs, but those are of a new format. They are the first 2 trials that look at a head-to-head comparison with hydroxyurea.

MPNs can be pretty tricky to diagnose. Do you foresee any advancements or improvements with diagnostic tools in the next couple of years?

The second part is that there is always some overlap between those myeloid diseases. There are MDS and MDS/MPN diseases. There is always that kind of continuum of those myeloid diseases, and sometimes the line is not that distinct between those categories. 

Advancement recently had been integrating some of the molecular data into the diagnostic criteria. If a patient has a JAK2 V617F mutation or calreticulan mutation, in a way that obviously excludes secondary or reactive. If a patient is having an infection, they will not have a clonal marker for the disease. In MPNs, we are a little bit ahead of MDS in integrating molecular data. Those are helpful in that setting.  

There are certain mutations that obviously will be more unique for a subtype. Now, the JAK2 does not distinguish a myeloproliferative myelofibrosis from ET or PV, because they're the same mutation. It can be seen in MDS/MPN, but it's not going to be seen in patients with MDS alone. 

Molecular testing definitely makes the diagnosis easier. The best example is probably PV. In the past, the main struggle was trying to distinguish it primarily from secondary polycythemia. We know that almost 98% of patients with PV would have a clonal marker. If it doesn’t, then we start to work out for less common hereditary causes of PV.

The good thing is that those tests are now very widely available now that they can be checked on peripheral blood that doesn’t even need a bone marrow test to be done. That’s how the progress was done, and the new criteria actually reflect that.

JAK2 is an important target now in MPNs. Are there any other emerging molecular abnormalities that can be targeted with potential therapies?

Even in the JAK/STAT pathway, I don’t think we completely unfolded the story there. As mentioned during my talk, the JAK/STAT pathway is the whole mark of the disease’s activation of that pathway. We’ve had 1 drug approved, but there had been other drugs where their development has not been as successful. There are opportunities to target the pathway itself by better JAK2 inhibitors and, in a way, second- or third-generation JAK2 inhibitors—medications that can target the downstream effect of the JAK2. 

Some of the efforts also recently had been trying to combine things with ruxolitinib (Jakafi) or JAK2 inhibitors. Ruxolitinib is the one approved commercially and is now available to patients. There are studies looking at Pim kinase, which seems to be an important pathway in patients with MPNs.

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