PF682 MULTICENTER RETROSPECTIVE STUDY EVALUATING FIBROSIS RISK IN PATIENTS WITH ET DEPENDING ON THE TREATMENT SCENARIO
Authors: Sobas M. , Olszewska‐Szopa M. , Nowak M. , Reszka K. , Drapniewski A. , Czyż J. , Szukalski L. , Golos A. , Masternak A. , Blanco A. Abuin , Encinas M. Perez , Casares M.T. Gomez , Pereira M.S. Noya , Wróbel T. 
Published: June 2019

Background:

The main objective of the treatment of essential thrombocythemia (ET) is to reduce thrombohemorrhagic events. According to last European LeukemiaNet (ELN) guidelines, hydroxycarbamide (HU) and interferon (IFN) are recommended as a first line therapy and anagrelide (ANA) is a second‐line therapy option in high‐risk patients with ET. According to the literature, ANA is not inferior to HU, but in some studies there was observed an association of ANA with a higher incidence of arterial thrombosis, bleeding complications and fibrotic progression. Thus, the panel of the ELN did not reached a consensus on recommending the ANA in first line therapy.

Aims:

to analyse the outcome of ET patients according to received therapy (ANA vs HU vs ANA plus HU vs no treatment)

Methods:

We performed the multicentre, retrospective study. The study was conducted in accordance with the Declaration of Helsinki. We analysed 993 ET patients diagnosed and treated between 1985 and 2017. Clinical and analytical data were collected at diagnosis (age, sex, WBC, Hgb, Plt, LDH, mutation status, karyotype, splenomegaly, IPSET, thrombosis previous at diagnosis). Patients with suspicious of prefibrotic fase of myelofibrosis (pre‐PMF), were excluded from the analysis. Patients were classified according to the therapy they received (HU, ANA, HU plus ANA, no therapy). The statistical analysis due the lack of normal distribution of variables was based on analysis of variance (ANOVA). The survival analysis was prepared using Kaplan‐Meier estimator.

Results:

There was 542 (54.6%) patients on HU, 117 (11.8%) on ANA, 75 (7.5%) on ANA plus HU, 33 (3.3%) with other therapy and 226 (22.8%) with no treatment. We did not find significant differences in clinical and analytical data at diagnosis between 4 groups of patients. The median follow‐up was 99 (> 12–354) months. Respect to the frequency of transformation to myelofibrosis, there was no significant differences between patients on ANA vs on HU (p = 0,848). However, we observed increased frequency of progression to myelofibrosis in patients on HU plus ANA vs no treatment (9.33 vs 3.54%; p = 0,046). There was no significant differences between patients on ANA vs no treatment and patients on HU vs no treatment. The overall survival free from fibrotic transformation (HU vs ANA vs HU plus ANA vs no treatment) is presented on a figure. Patients who presented fibrotic transformation vs no transformation had significantly higher LDH level at diagnosis (284.9 vs 246.7; p = 0.023). Moreover, fibrotic transformation was significantly more frequent in ET JAK2 (−) vs ET JAK2 (+) (8.9 vs 4.4; p = 0.057).

Summary/Conclusion:

There was no significant difference between fibrotic transformations in ET on HU vs ET on ANA. The risk of fibrotic transformation of ET seems to be related to analytical data and biological features previous to start the treatment but not with the therapy. The association between HU+ANA therapy and myelofibrosis transformation probably reflects a more advanced disease. Based on our data, contrary to previous observations, ANA does not seem to increase the risk of fibrosis. Concerning higher prevalence of fibrosis in HU+ANA ET therapy, further study is necessary to establish the safety of combined treatment.

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