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
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)
0.0
00
.25
0.5
00
.75
1.0
0
0 5 10 15 20Years from diagnosis
.
------ BM fibrosis 2.2% pts-yrNo BM fibrosis
0.8% pts-yr
IRR = 2.7, p=0.01
Barbui T et al, Blood 2012
Degree of bone marrow fibrosisto predict events in PVSG-ET
Campbell et al, JCO 2009
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
WHO-ET vs PMF: Prognostic Value
0,2%0,8%
9,3%
2,3%
12,3%
16,9%
0,0%
5,0%
10,0%
15,0%
20,0%
5-year CI 10-year CI 15-year CI
ET
PMF
Incidence of MF
0,2%0,7%
2,1%1,5%
5,8%
11,7%
0,0%
2,0%
4,0%
6,0%
8,0%
10,0%
12,0%
14,0%
5-year CI 10-year CI 15-year CI
ET
PMF
Incidence of AML
OS
Barbui et al, Leukemia 2013Barbui et al, J Clin Oncol. 2011 Aug 10;29(23):3179-84
3,0%
14,8%
24,6%
8,6%
24,4%
56,1%
0,0%
10,0%
20,0%
30,0%
40,0%
50,0%
60,0%
5-year CI 10-year CI 15-year CI
ET
PMF
Survival, Leukemic Transformation and Fibrotic Progression in Essential Thrombocythemia are significantly influenced by Accurate Morphologic Diagnosis
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
Cervantes F et al. Blood 2009;113:2895-901
31%
19%
14%
10%
5%
4%
4%
13%
Current risk stratification in PMF
IPSSLow riskNo factor
• Age > 60 years• Hb <10 g/dL• WBC >25 x109/L• Blasts ≥1% • Constit. symptoms
Intermediate-1 riskscore 1
Intermediate-2 riskscore 2
High riskscore ≥ 3
135 months
95 months
48 months
27 months
International Prognostic Scoring System to predict survival (IPSS)
22%
29%
28%
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