A Conversation with an MPN Specialist: Focusing on Myelofibrosis

MPN Advocacy & Education International spoke with Dr. John Mascarenhas, Mount Sinai, to discuss and answer questions about myelofibrosis.

[janetrogers]

As a MF patient with a CalR mutation I truly appreciate these videos. Many of my questions have been answered. Thank you

[MalikaBourne]

Dr. John Mascarenhas, , thank you for the down-to-earth patient-level explanations. It is really a gift to be able to explain a not so well known complex disease and drugs to treat it on a level that the patient can reiterate to family and friends an understanding of how the patient is being treated.

[MalikaBourne]

It looks like I picked a good time in history to get diagnosed with PV. So thank you to all of you who are dedicated to researching MF.
Fifty years ago my grandfather was finally diagnosed with leukemia. He had to retire from farming due to fatigue without a diagnosis until he had leukemia.
Since I have had lifelong weird fatigue and high HMB and HCT even after postpartum hemorrhage I figured that I would get leukemia as well - if that makes any sense. I only have PV diagnosed at age 68. I feel so bad for the hell my grandfather went through decades about a grown man feeling so much fatigue and no one being able to fix the problem.

[MrStarchild]

This video is a conversation with Dr. John Mascarenhas, a myelofibrosis specialist at Mount Sinai hospital, hosted by the MPN Advocacy & Education International organization. The discussion focuses on providing information and answering audience questions about myelofibrosis.

Key points about myelofibrosis:

- Myelofibrosis is one of the myeloproliferative neoplasms (MPNs), along with polycythemia vera and essential thrombocythemia. It is a rare bone marrow cancer that disrupts the body's normal production of blood cells.

- In myelofibrosis, the bone marrow is replaced by scar tissue, impairing the marrow's ability to produce normal blood cells. This leads to abnormalities in blood counts, constitutional symptoms like fatigue and night sweats, and spleen enlargement.

- Myelofibrosis can occur on its own (primary MF) or can develop later from polycythemia vera or essential thrombocythemia (secondary MF). In secondary MF, the disease progresses from a chronic phase to a more accelerated phase over time.

- Symptoms of MF include anemia (low red blood cells), enlarged spleen, constitutional symptoms, high white blood cell and platelet counts. Some patients experience blood clots, bone pain, and transformation to acute leukemia in advanced stages.

- The exact cause of MF is unknown, but abnormal stem cell behavior leads to overproduction of inflammatory cytokines, fibrosis in the marrow, extramedullary hematopoiesis, and other disruptions in blood cell production. Genetic mutations like JAK2, CALR and MPL are believed to contribute.

- Goals of therapy are to reduce troublesome symptoms, control blood cell counts, reduce spleen size, and improve quality of life. Curative options are limited, but stem cell transplant may be feasible for some younger, fit patients.

Treatment approaches covered:

- Ruxolitinib (Jakafi) was the first JAK inhibitor approved for MF. It targets the JAK-STAT signaling pathway to reduce spleen size, improve symptoms and survival. Side effects like low blood counts, infections, thrombosis must be monitored.

- Fedratinib (Inrebic) is a newer JAK inhibitor also used to treat spleen size and symptoms. Warnings exist for encephalopathy and worsening liver function.

- JAK inhibitors don't fix the underlying disease and are not curative therapies. They must be taken continuously to maintain benefits. Stopping can lead to rapid loss of response.

- Older drugs that may still be used include danazol, hydroxyurea and glucocorticoids to control blood counts short-term. Immunomodulators like lenalidomide may modestly help anemia. Chemotherapy is reserved for advanced disease.

- Stem cell transplant, while risky, remains the only cure currently. Transplant is typically done in younger patients without major comorbidities who have an appropriate donor. Outcomes have improved with better patient selection.

- Emerging treatment directions include PI3K inhibitors, hedgehog pathway inhibitors, telomerase inhibitors, anti-fibrosis agents, chimeric antigen receptor T-cell (CAR-T) therapy, and combination approaches. Research continues to find less toxic and more durable therapies.

Patient questions answered on the program cover topics like handling MF symptoms, diet and nutrition recommendations, the watch-and-wait approach, genetic testing, and real-world advice for newly diagnosed patients.

In summary, this presentation focuses on increasing general understanding of myelofibrosis biology, diagnosis, prognostic scoring systems, and the rationale behind current and emerging therapies. It provides an expert perspective on managing key symptoms like anemia and spleen enlargement. Discussion around future treatment directions gives patients and caregivers reason to be hopeful that progress is being made through ongoing research. As one of the rarer MPNs requiring specialized management, programs like this offer an important opportunity to educate and empower those impacted by myelofibrosis.

[beverlyann]

And I just heard you say "progression" and that's exactly what's happening to me now. Tomorrow I have an important appointment with my oncologist hematologist and though the BCR ABL test boom biopsies have come back was it progressing too BCR ABL 190 The doctor wants to keep me on Jakafi 25 mg. Could I have your email address and email you my concerns and get your input?