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Experience with ruxolitinib in the treatment of myelofibrosis and polycythaemia vera at Czech haematological institutions


Authors: B. Weinbergerová 1;  P. Čičátková 1;  M. Palová 2;  L. Stejskal 3;  P. Bělohlávková 4;  J. Kissová 5;  L. Walterová 6;  H. Fraňková 6;  O. Černá 7;  L. Lakomá 8;  M. Brejcha 9;  J. Pelková 10;  M. Schutzova 11;  J. Obernauerová 12;  D. Nechvílová 13;  E. Bogoczová 14;  A. Hluší 2;  E. Faber 2;  M. Penka 5;  Y. Brychtová 1;  L. Červinek 1;  M. Doubek 1;  P. Žák 4;  J. Mayer 1;  Z. Ráčil 1
Authors‘ workplace: Interní hematologická a onkologická klinika LF MU a FN Brno 1;  Hemato-onkologická klinika FN Olomouc 2;  Klinika hematoonkologie FN Ostrava a LF OU 3;  IV. Interní hematologická klinika FN a LF UK, Hradec Králové 4;  Oddělení klinické hematologie FN Brno 5;  Oddělení klinické hematologie Krajské nemocnice Liberec 6;  Interní hematologická klinika FNKV a LF UK, Praha 7;  Hematologická ambulance Nemocnice Havlíčkův Brod 8;  Hematologická ambulance Nemocnice Nový Jičín 9;  Hematologické a transfúzní oddělení Nemocnice Vsetín 10;  Hematologicko-onkologické oddělení FN Plzeň 11;  Hematologicko-transfúzní oddělení Nemocnice Mladá Boleslav 12;  Hematologicko-transfúzní oddělení Orlickoústecké nemocnice, Ústí nad Orlicí 13;  Hematologická ambulance Vítkovické nemocnice, Ostrava-Vítkovice 14
Published in: Transfuze Hematol. dnes,23, 2017, No. 1, p. 30-40.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Backgrounds:
Ruxolitinib, a Janus kinase 1 and 2 inhibitor, demonstrated efficacy in patients with myelofibrosis and polycythaemia vera in the randomized COMFORT-I, COMFORT-II and RESPONSE studies. Ruxolitinib demonstrated superior durable reduction of splenomegaly and disease-associated symptoms, maintenance of haematocrit values, improvement in quality of life and overall survival compared to placebo or best available therapy.

Material and Methods:
A retrospective analysis evaluated efficacy and tolerability of ruxolitinib in a cohort of unselected myelofibrosis and polycythaemia vera patients treated in routine clinical practice at 14 Czech haematological centres from 2013 to 2016.

Results:
Myelofibrosis – a total of 62 patients with myelofibrosis treated with ruxolitinib were evaluated. The most frequent indication for treatment was concurrent splenomegaly and constitutional symptoms in 54 (87.1%) cases. Reduction ≥ 1/3 in palpable spleen length was achieved in 43 (72.9%) patients with baseline splenomegaly at a median of 4 weeks after starting therapy. Constitutional symptoms receded in 38 (92.7%) of 41 patients at a median of 4 weeks after starting therapy. While on ruxolitinib, eleven (18.0%) patients developed grade 3–4 anaemia and thirteen (21.3%) patients developed grade 3–4 thrombocytopenia. Forty six (74.2%) patients survived. Twenty five (40.3%) patients discontinued therapy, most frequently due to inefficacy (16.1% of patients) or haematological toxicity (8.1% of patients). Median duration of ruxolitinib therapy was 41 weeks.

Polycythaemia vera – a total of 8 patients with polycythaemia vera treated with ruxolitinib because of resistance or intolerance of previous treatment was analysed. Six (75.0%) patients achieved complete remission. All patients experienced resolution of disease-associated symptoms. No patient developed grade 3 to 4 toxicity. At evaluation, all patients remained on ruxolitinib with a median duration of 32.5 weeks.

Conclusion:
Our analysis confirmed the very good treatment efficacy of ruxolitinib in patients with myelofibrosis and polycythaemia vera on reduction of splenomegaly and alleviation of disease-associated symptoms. Ruxolitinib additionally led to the correction of haematocrit values in patients with polycythaemia vera. Haematological toxicity was generally low.

KEY WORDS:
ruxolitinib – myelofibrosis – polycythaemia vera – treatment outcome – drug toxicity


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