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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
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)
0.50
0.75
1.00
.
------ BM fibrosis
0.25
2.2% pts-yr No BM fibrosis 0.8% pts-yr
0.00
IRR = 2.7, p=0.01
0
5
10 Years from diagnosis
15
Barbui T et al, Blood 2012
20
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
14,0%
Incidence of AML 11,7%
12,0%
Survival, Leukemic Transformation and Fibrotic Progression in Essential Thrombocythemia are significantly influenced by Accurate Morphologic Diagnosis
10,0% ET PMF 8,0% 5,8%
6,0%
OS 60,0%
4,0%
56,1%
2,1% 1,5%
2,0%
50,0% 0,7%
0,2%
ET PMF
0,0% 5-year CI
10-year CI
15-year CI
40,0%
30,0%
Incidence of MF
24,4%
20,0%
24,6%
20,0% 14,8% 16,9%
8,6%
10,0%
ET 15,0%
3,0%
PMF 12,3%
0,0% 5-year CI
10-year CI
15-year CI
9,3%
10,0%
5,0% 2,3% 0,2%
0,8%
0,0% 5-year CI
10-year CI
15-year CI
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% 4% 5% 10% 14% 19% 31%
Cervantes F et al. Blood 2009;113:2895-901
Current risk stratification in PMF Low risk
IPSS
No factor
Intermediate-1 risk • • • • •
Age > 60 years Hb 25 x109/L Blasts ≥1% Constit. symptoms
score 1
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
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