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

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.

• Authors: Francesca Palandri, Lucia Catani, Massimiliano Bonifacio, Giulia Benevolo, Florian Heidel, Giuseppe A Palumbo, Monica Crugnola, Elisabetta Abruzzese, Daniela Bartoletti, Nicola Polverelli, Micaela Bergamaschi, Mario Tiribelli, Alessandra Iurlo, Massimo Breccia, Francesco Cavazzini, Alessia Tieghi, Gianni Binotto, Alessandro Isidori, Bruno Martino, Mariella D'Adda, Costanza Bosi, Elena Sabattini, Umberto Vitolo, Franco Aversa, Adalberto Ibatici, Roberto M Lemoli, Nicola Sgherza, Antonio Cuneo, Giovanni Martinelli, Giampietro Semenzato, Michele Cavo, Nicola Vianelli, Maria R Sapienza, Roberto Latagliata
• Journal: British journal of haematology (Br J Haematol) Vol. 183 Issue 1 Pg. 35-46 (10 2018) ISSN: 1365-2141 [Electronic] England
• PMID: 30010187 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• Nitriles
• Pyrazoles
• Pyrimidines
• ruxolitinib
• Janus Kinases

Topics

• Age Factors
• Aged
• Genotype
• Humans
• Janus Kinases (antagonists & inhibitors)
• Mutation
• Nitriles
• Primary Myelofibrosis (drug therapy, genetics, mortality)
• Pyrazoles (therapeutic use)
• Pyrimidines
• Retrospective Studies
• Risk Factors
• Survival Analysis
• Treatment Outcome