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