Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome.
Marc G BergerBruno PereiraPhilippe RousselotPascale Cony-MakhoulMartine GardembasLaurence LegrosMartine Escoffre-BarbeFranck-Emmanuel NicoliniSandrine SauguesCéline LambertDelphine ReaAgnès Guerci-BreslerStéphane GiraudierJoëlle GuilhotSusanne SausseleFrançois-Xavier Mahonnull nullPublished in: British journal of haematology (2019)
The effectiveness of tyrosine kinase inhibitors (TKIs) has made it possible to consider treatment discontinuation in chronic myeloid leukaemia (CML) patients that achieve an excellent response. However, a few of the patients included in the Europe Stop Tyrosine Kinase Inhibitors (EURO-SKI) trial reported musculoskeletal pain shortly after stopping TKIs, considered as a withdrawal syndrome (WS). To identify factors that may predispose to TKI WS, we analysed the pharmacovigilance declarations for the 6 months after stopping TKIs in a large cohort of CML (n = 427) that combined the French patients included in the STop IMatinib 2 (STIM2; n = 224) and EURO-SKI (n = 203) trials. Among these patients, 23% (99/427) developed TKI WS after stopping imatinib (77/373; 20·4%), nilotinib (12/29; 41·4%) or dasatinib (10/25; 40%). WS concerned mainly the upper body joints, and required multiple symptomatic treatments in 30% of patients. Univariate and multivariate analyses identified two risk factors: duration of TKI treatment [risk ratio (RR) = 1·68 (1·02-2·74)] with a 93-month cut-off time, and history of osteoarticular symptoms [RR = 1·84 (1·04-3·28)]. These findings confirm that WS is a TKI class effect. CML patients should be carefully screened before treatment initiation to identify pre-existent osteoarticular symptoms. Moreover, before TKI discontinuation, patients should be informed of the possibility of WS, particularly after a long treatment period.
Keyphrases
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- prognostic factors
- risk factors
- randomized controlled trial
- clinical trial
- peritoneal dialysis
- tyrosine kinase
- systematic review
- immune response
- spinal cord
- bone marrow
- emergency department
- study protocol
- physical activity
- neuropathic pain
- data analysis
- electronic health record