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Br J Haematol. 2018 Oct;183(1):35-46. doi: 10.1111/bjh.15497. Epub 2018 Jul 16.

Ruxolitinib in elderly patients with myelofibrosis: impact of age and genotype. A multicentre study on 291 elderly patients.

Author information

1
Institute of Haematology "L. and A. Seràgnoli", Sant'Orsola-Malpighi University Hospital, Bologna, Italy.
2
Department of Medicine, Section of Haematology, University of Verona, Verona, Italy.
3
Division of Haematology, Città della Salute e della Scienza Hospital, Torino, Italy.
4
Internal Medicine II, Haematology and Oncology, Friedrich-Schiller-University Medical Centre, Jena, Germany.
5
Division of Haematology, AOU "Policlinico-V. Emanuele", University of Catania, Catania, Italy.
6
Division of Haematology, Azienda Ospedaliero-Universitaria di Parma, Udine, Italy.
7
Division of Haematology, Ospedale S. Eugenio, Roma, Italy.
8
Unit of Blood Diseases and Stem Cells Transplantation, Department of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili of Brescia, Brescia, Italy.
9
Clinic of Haematology, Department of Internal Medicine (DiMI), IRCCS AOU San Martino-IST, Genova, Italy.
10
Division of Haematology and BMT, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.
11
Haematology Division, IRCCS Ca' Granda - Maggiore Policlinico Hospital Foundation, University of Milan, Milan, Italy.
12
Division of Cellular Biotechnologies and Haematology, University Sapienza, Roma, Italy.
13
Division of Haematology, University of Ferrara, Ferrara, Italy.
14
Division of Haematology, Azienda Ospedaliera-IRCSS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
15
Unit of Haematology and Clinical Immunology, University of Padova, Padova, Italy.
16
Haematology and Stem Cell Transplant Centre, AORMN Hospital, Pesaro, Italy.
17
Division of Haematology, Azienda Ospedaliera 'Bianchi Melacrino Morelli', Reggio Calabria, Italy.
18
Division of Haematology, ASST Spedali Civili di Brescia, Brescia, Italy.
19
Division of Haematology, Piacenza hospital, Piacenza, Italy.
20
Division of Haematology and Bone Marrow Transplant, IRCCS San Martino-IST, Genova, Italy.
21
Division of Haematology, Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy.
22
IRCCs-IRST della Romagna, Meldola, Forlì, Italy.

Abstract

Ruxolitinib is a JAK1/2 inhibitor that may control myelofibrosis (MF)-related splenomegaly and symptoms and can be prescribed regardless of age. While aging is known to correlate with worse prognosis, no specific analysis is available to confirm that ruxolitinib is suitable for use in older populations. A clinical database was created in 23 European Haematology Centres and retrospective data on 291 MF patients treated with ruxolitinib when aged ≥65 years were analysed in order to assess the impact of age and molecular genotype on responses, toxicities and survival. Additional mutations were evaluated by a next generation sequencing (NGS) approach in 69 patients with available peripheral blood samples at the start of ruxolitinib treatment. Compared to older (age 65-74 years) patients, elderly (≥75 years) showed comparable responses to ruxolitinib, but higher rates of drug-induced anaemia and thrombocytopenia and worse survival. Nonetheless, the ruxolitinib discontinuation rate was comparable in the two age groups. Number and types of molecular abnormalities were comparable across age groups. However, the presence of high molecular risk (HMR) mutations significantly affected survival, counterbalancing the effect of aging. Indeed, elderly patients with <2 HMR mutated genes had a comparable survival to older patients with ≥2 HMR mutations. Given that responses were not influenced by age, older age per se should not be a limitation for ruxolitinib administration. NGS analysis of HMR mutations also confirmed a strong predictive value in elderly patients.

KEYWORDS:

elderly; high molecular risk; high molecular risk mutations; myelofibrosis; ruxolitinib

PMID:
30010187
DOI:
10.1111/bjh.15497
[Indexed for MEDLINE]

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