Rami S. Komrokji, MD
A growing understanding about the underlying biology of myelofibrosis has helped improve the diagnosis and treatment of the disease during the past decade and is paving the way for further advancements, according to a panel of experts in the field. “We’ve learned more about the disease biology in the last 5 to 10 years than we did over the 50 years prior, and hopefully, within the next few years, we will have more effective treatments for patients,” Rami S. Komrokji, MD, said during a recent OncLive Peer Exchange®
Today, approaches for treating patients are more closely matched with the characteristics of the malignancy, noted Ruben A. Mesa, MD, FACP, of UT Health San Antonio MD Anderson Cancer Center, who headed the effort to develop the first National Comprehensive Cancer Network (NCCN) Guidelines for myelofibrosis and other myeloproliferative neoplasms (MPNs) in 2017.
“I’m incredibly hopeful. Certainly during my career, I’ve witnessed a change in MPNs from largely using agents for which we did not really have a strong scientific rationale. They were empirically being used from development from other indications,” Mesa said.
MPNs are a rare group of chronic blood cancers associated with dysregulation of the JAK2-STAT5 signaling pathway.1,2
Myelofibrosis is the least common but most aggressive of the Philadelphia chromosome–negative MPNs, a group that also includes polycythemia vera (PV) and essential thrombocythemia (ET). Individuals can develop primary myelofibrosis (PMF), which includes prefibrotic or early PMF (pre-PMF) and overt PMF,3
or myelofibrosis can result from progression of ET or PV.1,4
Mesa said the US incidence of primary myelofibrosis is approximately 1 per 100,000 cases per year, according to a database study he and his colleagues conducted.4 Because patients with myelofibrosis frequently survive several years after diagnosis, the estimated prevalence is much higher than the incidence would suggest (4-6 per 100,000).4,5
Harry P. Erba, MD, PhD, who moderated the panel of distinguished MPN researchers, noted that although significant overlap exists between MPN subtypes, each has distinct biological characteristics that guide diagnosis and treatment decisions. Allogeneic stem cell transplant (ASCT) is the only curative treatment for myelofibrosis, but its life-threatening risks render many patients ineligible for transplant. “As we learn more about the biology, hopefully, we’re going to move more toward targeted agents directed at the biology,” he said. The identification of JAK2
as a driver mutation in myelofibrosis led to FDA approval in 2011 of ruxolitinib (Jakafi), the first targeted therapy for myelofibrosis. The panel reviewed data from clinical trials of ruxolitinib and discussed other targeted agents in the pipeline. They also talked about important considerations for incorporating ruxolitinib into practice.
Accurately diagnosing myelofibrosis is essential before selecting treatment. In 2016, the World Health Organization (WHO) developed updated criteria for classifying MPNs with the goal of making it easier for clinicians to distinguish between ET, PV, and PMF.3 Srdan Verstovsek, MD, PhD, said the criteria make it clear that strong clinical suspicion is not sufficient to diagnose myelofibrosis. “A combination of tests is required to make the diagnosis,” he said, noting that 2016 WHO guidelines emphasize the necessity of a bone marrow biopsy. Biopsy results in a patient with overt PMF will show proliferation of atypical megakaryocytes accompanied by grade 2 or 3 reticulin and/ or collagen fibrosis. He said other essential tests include genetic screening for a JAK2, CALR,
mutation and a complete blood cell count. Verstovsek said anemia, an elevated serum lactate dehydrogenase level, leukoerythroblastosis in the peripheral smear, leukocytosis, splenomegaly, and constitutional symptoms are all minor criteria used to make a diagnosis.3
Mesa said he often has patients referred to him with a diagnosis of myelofibrosis based on biopsy results showing fibrosis in the bone marrow. “I see this all the time…but fibrosis does not mean myelofibrosis as a disease entity. It needs to be worked up,” he said. The panel discussed how fibrosis also occurs with myelodysplastic syndromes, chronic myeloid leukemia, or other myeloid neoplasms, which must be ruled out when diagnosing PMF.