Customize
Quick Links
Specialties

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. These activites are not approved for AMA PRA Category 1 Credit

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Incyte Corporation.

Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care PER Pulse™ Recap

PER Pulse Recap

PER Pulse™ Recap


1 of 3
PER Pulse™ Recap

The live continuing medical education activity, Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing best practices in managing myeloproliferative neoplasms (MPNs): Ruben A. Mesa, MD, FACP; Daniel J. DeAngelo, MD, PhD; John Mascarenhas, MD; and Michael J. Mauro, MD. This program featured 4 cutting-edge lectures on the pathogenesis and diagnosis of, and emerging treatment options for, some of the most common MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, followed by an engaging panel discussion on the multifaceted management of patients with these diseases. This first of 3 PER Pulse™ Recaps reviews the pathogenesis of MPNs.

Below are some highlights from Dr. Mauro’s lecture:

  • There are 3 primary driver mutations in MPNs, each of which impacts survival:
    • The JAK2 V617F driver mutation was discovered in 2005 and is present in ~95% of all PV cases and in ~50% to 60% of all ET and myelofibrosis cases.
      • This mutation produces ligand-independent JAK2 signaling that increases proliferation and differentiation of hematopoietic progenitor cells and is a negative prognostic factor.
    • The MPL515 mutation in the thrombopoietin receptor is the least frequent of the driver mutations, being present in 3% to 6% of ET cases and 8% to 10% of myelofibrosis cases and absent altogether in PV.
      • The MPL515 mutation leads to constitutive activation of the Mpl protein and is a negative prognostic factor.
    • The CALR mutation is another driver mutation. It is present in <10% of ET cases, ~15% of myelofibrosis cases, but absent in PV.
      • The CALR mutation produces mutant calreticulin. Although the exact pathogenic mechanism has not been resolved, mutated calreticulin does appear to bind to Mpl and activate the JAK/STAT pathway. Its presence is a favorable prognostic factor.
    • Patients with triple-negative disease (negative for JAK2, MPL515, and CALR mutations), who account for 10% to 25% of all cases, have the worst prognosis.
  • In addition, there are several nondriver mutations that are also present in MPNs, including ASXL1, EZH2, SRSF2, and IDH1-2. The presence of any of these mutations negatively impacts survival.

For additional commentary about this topic and the Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care symposium, please visit www.gotoper.com.


2 of 3
PER Pulse™ Recap

The live continuing medical education activity, Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing best practices in managing myeloproliferative neoplasms (MPNs): Ruben A. Mesa, MD, FACP; Daniel J. DeAngelo, MD, PhD; John Mascarenhas, MD; and Michael J. Mauro, MD. This program featured 4 cutting-edge lectures on the pathogenesis, diagnosis, and emerging treatment options for some of the most common MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, followed by an engaging panel discussion on the multifaceted management of patients with these diseases. This second of 3 PER Pulse™ Recaps reviews the diagnosis and risk stratification of MPNs.

Below are some highlights from Dr. DeAngelo’s lecture:

  • A diagnosis of PV requires (1) elevated hemoglobin, elevated hematocrit, or increased red cell mass; (2) bone marrow findings of hypercellularity with panmyelosis, including pleomorphic mature megakaryocytes; and (3) either JAK2 mutation or subnormal erythropoietin level.
    • The definition of a complete response to PV therapy includes all of the following: hematocrit <45% (without phlebotomy), platelet count ≤400 x 109/L, white blood cell count ≤10 x 109/L, normal spleen size on imaging, and no disease-related symptoms.
    • Patients with PV are stratified into low-risk disease (age <60 and no history of thrombosis) and high-risk disease (age ≥60 or previous thrombosis).
    • The European LeukemiaNet has the following indications for cytoreductive therapy with hydroxyurea or interferon: (1) high-risk disease, (2) frequent phlebotomy requirement, (3) platelets >1500 x 109/L, and (4) progressive leukocytosis.
  • A diagnosis of ET requires (1) elevated platelet count, (2) bone marrow findings of abnormal megakaryocyte proliferation, (3) exclusion of diagnoses of other related disorders, and (4) presence of a specific mutation (JAK2, CALR, or MPL), presence of a clonal marker, or absence of evidence for reactive thrombocytosis.
    • In patients with ET, the risk of thrombosis is stratified into high risk (age ≥60 or previous thrombosis), low risk (age <60, no history of thrombosis, and platelet count <1 million), and low risk with extreme thrombocytosis (in which platelet count >1 million), which may have even lower thrombotic risk.
  • A diagnosis of post-PV or post-ET myelofibrosis requires previous diagnosis of PV or ET and grade 2 or 3 bone marrow fibrosis on a 0-3 scale or grade 3 or 4 fibrosis on a 0-4 scale. In addition, 2 of the remaining criteria are required: anemia, leukoerythroblastosis, worsening splenomegaly, constitutional symptoms, and increased serum lactose dehydrogenase level (post-ET disease only).
    • The Dynamic International Prognostic Scoring System for Primary Myelofibrosis (DIPSS) Plus uses 8 risk factors to predict survival: age >65, hemoglobin <10 g/dL, leukocytes >25 x 109/L, circulating blasts ≥1%, constitutional symptoms, red blood cell transfusion dependency, platelet count <100 x 109/L, and unfavorable karyotype.
    • Patients with myelofibrosis have a median survival time of 5.75 years.
    • Seven mutations have been identified that predict poor prognosis among patients with myelofibrosis: ASXL1, SRSF2, CBL, KIT, RUNX1, SH2B3, and CEBPA. Patients with these mutations have a median survival of only 3.6 years.

For additional commentary about this topic and the Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care symposium, please visit www.gotoper.com.


3 of 3
PER Pulse™ Recap

The live continuing medical education activity, Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care, held adjunct to an annual oncology meeting in Chicago, Illinois, featured the following experts discussing best practices in managing myeloproliferative neoplasms (MPNs): Ruben A. Mesa, MD, FACP; Daniel J. DeAngelo, MD, PhD; John Mascarenhas, MD; and Michael J. Mauro, MD. This program featured 4 cutting-edge lectures on the pathogenesis, diagnosis, and emerging treatment options for some of the most common MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis, followed by an engaging panel discussion on the multifaceted management of patients with these diseases. This third of 3 PER Pulse™ Recaps describes evolving therapeutic options for patients with MPNs.

Below are some highlights from Dr. Mascarenhas’ lecture:

  • The phase III ARETA trial of anagrelide versus placebo in ET demonstrated that anagrelide produced superior 1-year event-free survival (87% vs 69%; HR, 0.356; P = .0008).
  • In an interim analysis of the randomized MPD-RC 112 trial in patients with high-risk PV or ET treated with either hydroxyurea or weekly pegylated interferon (IFN), no significant differences in either overall response rate or molecular response were observed between arms. Pegylated IFN appeared to have more safety concerns, however.
  • The phase III PROUD-PV study demonstrated noninferiority of biweekly ropeginterferon alfa-2b compared with hydroxyurea in complete hematologic response rate (43.1% vs 45.6%; P = .0028). In addition, ropeginterferon showed evidence of a more favorable safety profile than hydroxyurea among patients with PV.
  • Pacritinib, a JAK inhibitor, was compared with best available therapy (including ruxolitinib) in the phase III PERSIST-2 trial in patients with myelofibrosis and thrombocytopenia. Results suggest that pacritinib administered twice daily was superior in both spleen volume and symptom reduction compared with best available therapy, but this was not true for once-daily pacritinib.
  • Momelotinib, another JAK inhibitor, was compared with ruxolitinib in the phase III Simplify 1 trial in patients with myelofibrosis. Momelotinib met the primary noninferiority endpoint of spleen volume reduction at 24 weeks (26.5% vs 29.0%; P = .011), but it did not meet the secondary endpoint of total symptom score reduction.
  • PRM-151, or recombinant human pentraxin-2, is an endogenous regulator of tissue repair that has been shown to prevent and reverse fibrosis in preclinical models. In a phase I and extension study of PRM-151 alone or in combination with ruxolitinib, 9 of 13 patients achieved at least a 50% reduction in symptoms at 72 weeks and 9 of 10 evaluable patients had spleen reductions.
  • Other agents that have demonstrated activity in MPNs are idasanutlin, an MDM2 inhibitor; LCL161, a second mitochondrial-derived activator of caspases (SMAC) mimetic; sotatercept, an activin inhibitor; and imetelstat, a telomerase inhibitor.

For additional commentary about this topic and the Expert Insights on the Management of Myeloproliferative Neoplasms: Evidence-Based Approaches and Emerging Strategies to Address Challenges in Care symposium, please visit www.gotoper.com.

PER® Practice Pulse
Practice Pattern Questions
How often do you attend society oncology/hematology meetings? (ASCO, ASH, SABCS)
Practice Pattern Questions
What is the most significant barrier to implementing new information in your clinical practice?






Become a Member

Forgot Password?
Calendar of Events
SUNMONTUESWEDTHURSFRISAT
     12
3456789
10111213141516
17181920212223
24252627282930
31
Filter By