Myelofibrosis-Associated Complications and Future Therapies

Jamile Shammo, MD:Patients with myelofibrosis end up with tremendous splenomegaly, and that causes a great deal of weight loss, early satiety, a loss of muscle mass, and a significant amount of bone pain. And, of course, they deal with the consequences of bone marrow failure, so they end up being anemic, thrombocytopenic, and perhaps neutropenic at times. And they would be more at risk for infections or complications from transfusions for their anemia. And so, it’s a very difficult disease to have. I think that we need to utilize all the drugs that we have in our armamentarium, so that we can perhaps improve patients’ quality of life.

There are a lot of clinical trials that are addressing novel agents for the treatment of myelofibrosis, and most of those trials are looking at patients who have failed ruxolitinib, which is the only FDA-approved drug for the treatment of this disorder. So, you have various JAK2 inhibitors, perhaps some that are more JAK2 specific and some may have FLT3 specificity. And then there’s also a whole slew of combination trials that are combining ruxolitinib together with other agents, for example, immune modulators, interferons, HDAC inhibitors, mTOR inhibitors, or PI3-kinase-delta inhibitors. There is a whole slew of novel agents and novel combinations. And I think it’s going to be very interesting to see the results of those trials moving forward.

When it comes to myelofibrosis, I think it’s very important to understand a little bit more about the disease biology. Why does it happen in the first place? What governs its progression? How can we utilize drugs effectively, such that we wouldn’t be compromising patients’ quality of life and we can actually enhance it? And when patients fail available therapy, how can we sort of personalize the next treatment option that they have? And how can we pick the best next drug? I think these are all questions that we need to answer in the future.

I think myelofibrosis is a serious disease. It’s a hematological neoplasm that deserves to be assessed appropriately, and patients need to be evaluated periodically. We need to do a better job at assessing their symptomatology and also offer patients with this entity treatment options that will improve their quality of life. I’m very hopeful for the future that perhaps we will be able to offer those patients many more treatment options.

Transcript edited for clarity.

June 2016

• A 72-year old male presents to his primary care physician with fatigue, abdominal pain lasting 3 months, and night sweats
• PMH includes depression and gout
• Physical Exam: BP, 155/85; spleen palpable 6 cm below costal margin
• Laboratory values:
  • Hb= 9.8 g/L
  • HCT= 38%
  • WBC= 22.3 x10⁹/L
  • Platelets= 255 x10⁹/L
• Bone marrow biopsy:
  • Megakaryocytic proliferation and atypia with evidence of reticulin fibrosis
• Blood smear showed leukoerythroblastosis
• Genetic testing showsJAK2 V617Fmutation
• Diagnosis: Primary myelofibrosis