Rami Komrokji, MD:Welcome to thisTargeted Oncology™ presentation on the “Evolving Role of JAK Inhibitors in Myelofibrosis and Beyond.”
I am Dr Rami Komrokji, the vice chair of the malignant hematology department and section head of leukemia and MDS [myelodysplastic syndrome] at Moffitt Cancer Center in Tampa, Florida. Joining me today is my colleague Dr Prithviraj Bose, an associate professor of the department of leukemia in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas.
In recent years, the identification of pathways and molecular targets have paved the way for the emergence of JAK inhibition for the treatment of myelofibrosis and other diseases. Today we will discuss the mechanism of action of available JAK inhibitors and their evolving role in the treatment landscape for myeloproliferative neoplasms.
Thank you for joining us, and let’s begin. Prithvi, welcome to Orlando, [Florida]. Good to see you.
Prithviraj Bose, MD:Thank you, same here.
Rami Komrokji, MD:Do you mind giving us a brief overview of myeloproliferative diseases, the role of the JAK/STAT pathway, and what the current unmet needs are in treatment?
Prithviraj Bose, MD:The classic MPNs [myeloproliferative neoplasms] are polycythemia vera, essential thrombocythemia, and primary myelofibrosis. And polycythemia vera and essential thrombocythemia can also progress to myelofibrosis. Sometimes we call that secondary myelofibrosis. The JAK-STAT pathway is universally activated in all the classic MPNs, regardless of the driver mutation status.
Most patients with polycythemia vera will have a mutation inJAK2. In fact, virtually everybody, about 99%, will have some mutation inJAK2, mostly V617F, some will have exon 12. In ET [essential thrombocytopenia] and primary myelofibrosis, about 60% will have theJAK2V617F mutation, about 30%, or 20% to 30%, will have a mutation inCALRand exon 9, and a few percent, about 5% will have a mutation inMPL, usually W515. There are a few cases that are triple negative, which means that they don’t have any of these identified driver mutations.
Rami Komrokji, MD:I totally agree, and I think you bring important points. One is mentioning that the JAK/STAT pathway is universal. The hallmark of the activation of the pathway is the hallmark in the disease.
Prithviraj Bose, MD:Exactly.
Rami Komrokji, MD:I think the point I always try to make is the activation could be not just because of the mutations but because of excessive signaling through the pathway. I still get asked the question, if somebody isJAK2negative, can they be helped using JAK2 inhibitors? And the answer obviously is yes for that.
Prithviraj Bose, MD:Yes.
Rami Komrokji, MD:The way I also see sometimes unmet needs, or like the way that I try to decide on management for patients, is really looking at what’s the clinical burden of the disease. I think most of the patients have splenomegaly, constitutional symptoms. Some patients have cytopenia. It gets more challenging when they are combined together or the accelerated phase of the disease, and that’s how I try to think of the management for those patients.
Prithviraj Bose, MD:It’s a needs-oriented approach.
Rami Komrokji, MD:Absolutely.
Transcript edited for clarity.