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 <10 g/dL
WBC >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