Tiziano Barbui MD Ospedale Papa Giovanni XXIII Bergamo, Italy Emerging JAK Inhibitors in Myelofibrosis: Determining the Right Agent for the Right Patient.(Madrid) How to use prognosis assessment criteria for MF management in the clinical practice Tiziano Barbui MD Ospedale Papa Giovanni XXIII Bergamo, Italy

FROM PV and ET to MYELOFIBROSIS: The value of bone marrow morphology

Bone marrow fibrosis (reticulin=>1): Yes: 74 pts ( 14%) INITIAL BONE MARROW RETICULIN FIBROSIS IN POLYCYTHEMIA VERA EXERTS AN IMPACT ON CLINICAL OUTCOME (IWG-RT study)   Tiziano Barbui1† , Jürgen Thiele,2† Francesco Passamonti,3 Elisa Rumi,4 Emanuela Boveri,4 Maria Luigia Randi,5 Irene Bertozzi,5 Filippo Marino,5 Alessandro M. Vannucchi,6 Elisabetta Antonioli,6 Valentina Carrai,6 Heinz Gisslinger,7 Veronika Buxhofer-Ausch,7 Leonhard Müllauer,8 Guido Finazzi,1 Alessandra Carobbio,1 Andrea Gianatti,1 Marco Ruggeri,9 Francesco Rodeghiero,9 Emanuele D’Amore,9 Alessandro Rambaldi,1 and Ayalew Tefferi,10 † 526 patients with strictly defined WHO diagnosis of PV Reviewer: JuergenThiele ;Participant centers (Bergamo, Pavia, Padova, Vicenza, Firenze, Vienna) Follow-up, years 5.3 (0-29.8) Bone marrow fibrosis (reticulin=>1): Yes: 74 pts ( 14%) No: 452 pts (86%)

Overt myelofibrosis-free survival (35 events) ------ BM fibrosis 2.2% pts-yr No BM fibrosis 0.8% pts-yr IRR = 2.7, p=0.01 Barbui T et al, Blood 2012

Degree of bone marrow fibrosis to predict events in PVSG-ET N= 361 patients Fibrosis grade (0 to 4) # grade 0-1: 135 # grade 2: 146 # grade 3-4: 80 Bone marrow fibrosis at diagnosis predicts Campbell et al, JCO 2009

WHO-ET vs PMF: Prognostic Value

Incidence of AML OS Incidence of MF Survival, Leukemic Transformation and Fibrotic Progression in Essential Thrombocythemia are significantly influenced by Accurate Morphologic Diagnosis Incidence of AML OS Incidence of MF Barbui et al, Leukemia 2013 Barbui et al, J Clin Oncol. 2011 Aug 10;29(23):3179-84

CLINICAL OVERT MYELOFIBROSIS: How to stratify patients to select therapy

Improving Survival Trends in PMF Median survival: 4.6 versus 6.5 y Cervantes et al. JCO 2012

Causes of Death in PMF 13% 4% 5% 10% 14% 19% 31% Cervantes F et al. Blood 2009;113:2895-901 31% 19% 14% 10% 5% 4% 13%

Current risk stratification in PMF Low risk No factor IPSS Intermediate-1 risk score 1 Age > 60 years Hb <10 g/dL WBC >25 x109/L Blasts ≥1% Constit. symptoms Intermediate-2 risk score 2 High risk score ≥ 3

International Prognostic Scoring System to predict survival (IPSS) 135 months 22% 95 months 29% 48 months 28% 27 months 21% Cervantes et al, Blood 2008

DINAMIC IPSS (DIPSS)

HEPATO-SPLENOMEGALY is not included in the risk classification of MF

CLINICAL OVERT MYELOFIBROSIS: Predictors of blast phase

Myelofibrosis: Prognosis assessment in clinical practice PMF risk stratification is based on IPSS and DIPSS, but cytogenetics and transfusional status may be a compendium Novel prognostic variables deserve further investigations on a large scale