Ruben A. Mesa, MD
The National Comprehensive Cancer Network (NCCN) published its first set of guidelines for myeloproliferative neoplasms1
(MPNs) in October 2016 and is already looking to update and expand these guidelines to match the need for direction in diagnosing and treating patients with MPNs.
The guidelines initially focused on diagnosing each of the MPNs and treatment options for patients with myelofibrosis, as that was the disease type with the greatest unmet need, Ruben A. Mesa, MD, explained in an interview with OncologyLive®
following his presentation at the 2017 NCCN Annual Conference.
“The myeloproliferative neoplasms were probably one of the most significant of the hematologic malignancies that did not yet have NCCN guidelines,” said Mesa, a professor of medicine and chair of hematology at Mayo Clinic in Phoenix, Arizona, and chair of the panel for the NCCN guidelines on MPNs. “The guidelines are very helpful in terms of improving quality of care by providing more homogeneity of care in the United States, trying to bring in current evidence regarding treatment that can be utilized, as well as clarifying the role of a variety of things, ranging from transplantation to therapies.”
The guidelines look to explain the criteria for diagnosing each of the MPNs, including the World Health Organization’s recent update to the classification of MPNs, and risk assessment. Yet the current edition of the guidelines only included current treatment options for patients with myelofibrosis. Treatment guidelines for patients with polycythemia vera or essential thrombocythemia are expected in the update, which Mesa remarked is expected in the summer of this year.
The myelofibrosis guidelines incorporate scoring systems for risk stratification, including the International Prognostic Scoring System (IPSS), the Dynamic IPSS (DIPSS), and the DIPSS-Plus. Mesa also noted that the guidelines endorse the 2013 International Working Group for Myelofibrosis Research and Treatment and European LeukemiaNet consensus response criteria, as well as the scoring system for total symptom burden.
“In myelofibrosis, there are clinical improvement criteria that can stand alone. You can have reduction in splenomegaly that counts as a response. What that leads to for clinical decision making is more subtle, and like all of these guidelines, they are married to clinical experience and expertise in terms of the character of response and how that balances against any negatives that come with the treatment in terms of side effects or toxicities as well as expense,” he said.
The guidelines also describe the prognostic significance of several common mutations in patients with primary myelofibrosis. Patients with an MPL
W515L/K mutation, for example, have a higher risk of thrombosis compared with patients who have a CALR
mutation, and they usually have an intermediate prognosis. Those who do not have JAK2
, or CALR
mutations have an inferior prognosis compared to patients with these driver mutations, with lower leukemia-free and overall survival rates. Patients with TP53
mutations are associated with a greater risk for transformation to acute myeloid leukemia (Table).
Table. Significance of Mutations in Patients With Primary Myelofibrosis
For patients with low-risk asymptomatic myelofibrosis, the guidelines recommend either observation for signs and symptoms of disease progression or a clinical trial. For symptomatic patients who are low-risk, the guidelines suggest interferons, a clinical trial, or ruxolitinib (Jakafi), the only FDA-approved targeted agent for patients with myelofibrosis. Ruxolitinib, a JAK1/2 inhibitor, is also recommended for patients with intermediate-1 and -2 disease, especially for those with intermediate-2 disease who are not candidates for transplant and have a high platelet count.
In a retrospective analysis of patients with myelofibrosis treated with ruxolitinib, patients with low-risk disease experienced a substantial improvement in symptoms.2
The proportion of patients with moderate to severe splenomegaly reduced from 64% to 16% with treatment and the rate for patients with moderate to severe fatigue decreased from 90% to 37%. Similar findings were noted in patients with intermediate-1–risk with a reduction in splenomegaly proportion from 53% to 10% and in the proportion of fatigue from 76% to 42%.
A pooled analysis from the COMFORT-I and COMFORT-II studies demonstrated that patients with intermediate-2- or high-risk myelofibrosis had an improved overall survival rate from treatment with ruxolitinib.3