Emerging diagnostic and risk stratification criteria

Transcription

1 PV STATE OF MIND Polycythemia vera: Emerging diagnostic and risk stratification criteria Rami S. Komrokji, MD Moffitt Cancer Center, Tampa, Florida

2 Disclosure These slides were developed by Incyte Corporation from an interview with Rami S. Komrokji, MD, conducted on May 4, Dr Komrokji was compensated for his participation in this interview. He has also received clinical research funding and served as a consultant for Incyte Corporation (Wilmington, DE).

3 Introduction to polycythemia vera (PV) A Philadelphia chromosome negative myeloproliferative neoplasm (MPN) 1,2 Characterized by trilineage hyperproliferation 3 White blood cells Multipotent progenitor cell Red blood cells Platelets References: 1. Vardiman JW et al. Blood. 2009;114(5): Tefferi A et al. Leukemia. 2008;22(1): Spivak JL. Blood. 2002;100(13):

4 Clinical features of PV at presentation Most patients present with 1 of 3 clinical scenarios 1 Diagnosis after a thrombotic event Diagnosis following presentation with disease-related symptoms Diagnosis by chance after routine blood work Initial presentation Asymptomatic Thrombosis Disease-related symptoms or splenomegaly Reference: 1. Passamonti F. Blood. 2012;120(2):

5 Erythrocytosis is the most prominent characteristic of PV 1 In 1,545 patients with PV, in addition to erythrocytosis 2 : 49% presented with leukocytosis 53% presented with thrombocytosis References: 1. Spivak JL. Ann Intern Med. 2010;152(5): Tefferi A et al. Leukemia. 2013;27(9):

6 PV diagnostic criteria: Erythrocytes World Health Organization (WHO) 1 Hemoglobin (Hb) levels Men >18.5 g/dl Women >16.5 g/dl or Hb or Hct >99th percentile of reference range for age, sex, or altitude of residence or Hb >17 g/dl (men) or >15 g/dl (women) if associated with a sustained increase of 2 g/dl from baseline that cannot be attributed to correction of iron deficiency or Elevated red cell mass >25% above mean normal predicted value British Committee for Standards in Haematology (BCSH) 2 Hematocrit (Hct) levels Men >52% Women >48% or Elevated red cell mass >25% above mean normal predicted value or Hct 60% (men) or 56% (women) in the absence of JAK2 mutation References: 1. Tefferi A et al. Leukemia. 2008;22(1): McMullin MF et al. Br J Haematol. 2007;138(6):

7 Hb and Hct are surrogates for red cell mass (RCM) 1 RCM and plasma volume may vary independently of each other 2 As the RCM expands, the plasma volume may also expand Hb and Hct levels might appear normal despite elevated RCM PV might not be apparent, even though the RCM may be elevated References: 1. Barbui T et al. Leukemia. 2014;28(6): Spivak JL. Blood. 2002;100(13):

8 Patients may have an elevated RCM without meeting Hb or Hct criteria for PV Patients With RCM 25% Higher Than the Mean Predicted Value but not Meeting Hb or Hct Criteria for PV Johansson et al, Hb 37 of 77 patients (48%) Cassinat et al, Hb 33 of 71 patients (46%) Alvarez-Larrán et al, Hb Hct 53 of 114 patients (46%) 21 of 114 patients (18%) Silver et al, Hb or Hct 8 of 28 patients (29%) References: 1. Johansson PL et al. Br J Haematol. 2005;129(5): Cassinat B et al. Leukemia. 2008;22(2): Alvarez-Larrán A et al. Haematologica. 2012;97(11): Silver RT et al. Blood. 2013;122(11):

9 Proposed revisions to diagnostic criteria for PV 1 Major Hb >16.5 g/dl for men, >16 g/dl for women Hct >49% for men, >48% for women Elevated RCM >25% above mean normal predicted value Bone marrow trilineage myeloproliferation with pleomorphic megakaryocytes Presence of JAK2V617F or JAK2 exon 12 mutation Minor Subnormal serum erythropoietin level If adopted, PV diagnosis would require meeting either all 3 major criteria or the first 2 major criteria and 1 minor criterion. Reference: 1. Tefferi A et al. Leukemia. 2014;28(7):

10 Stratification to predict risk for thrombosis and guide disease management 1* High risk Age >60 years or Previous thrombotic event Low risk Age 60 years and No history of thrombosis Does not predict survival, disease progression, or risk for leukemic/fibrotic transformation * In the absence of extreme thrombocytosis (platelets >1, /L). Reference: 1. Tefferi A et al. Am J Hematol. 2015;90(2);

11 Emerging evidence for additional risk factors Risk Factors for Possible Use in Models to Predict Survival, Disease Progression, or Hematologic/Fibrotic Transformation Erythrocytosis Marchioli et al, Leukocytosis Landolfi et al, Gangat et al, Chou et al, Lim et al, Bonicelli et al, Marchioli et al, Tefferi et al, Barbui et al, Thrombocytosis Alvarez-Larrán et al, Mutational profile Vannucchi et al, Passamonti et al, Hydroxyurea resistance Alvarez-Larrán et al, References: 1. Marchioli R et al. N Engl J Med. 2013;368(1): Landolfi R et al. Blood. 2007;109(6): Gangat N et al. Br J Haematol. 2007;138(3): Chou YS et al. Eur J Haematol. 2013;90(3): Lim Y et al. Thromb Res. 2015;135(5): Bonicelli G et al. Br J Haematol. 2013;160(2): Tefferi A et al. Leukemia. 2013;27(9): Barbui T et al. Blood. 2015;126(4): Alvarez-Larrán A et al. Blood. 2012;119(6): Vannucchi AM. Leukemia. 2007;21(9): Passamonti F et al. Leukemia. 2010;24(9):

12 Conclusions Revised diagnostic criteria that lower thresholds for Hb and Hct levels may identify PV in some patients with borderline red cell parameters who may be at increased risk for thrombotic events Standard risk factors (age >60 years and history of thrombosis) will maintain their significance but are not prognostic for disease progression or overall survival Investigators continue to explore the associations of various potential risk factors with outcomes in PV 2015, Incyte Corporation. All rights reserved. EDU-1288l 10/15