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Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome
Author(s) -
Berger Marc G.,
Pereira Bruno,
Rousselot Philippe,
ConyMakhoul Pascale,
Gardembas Martine,
Legros Laurence,
EscoffreBarbe Martine,
Nicolini FranckEmmanuel,
Saugues Sandrine,
Lambert Céline,
Réa Delphine,
GuerciBresler Agnès,
Giraudier Stéphane,
Guilhot Joëlle,
Saussele Susanne,
Mahon FrançoisXavier
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.16083
Subject(s) - medicine , discontinuation , dasatinib , imatinib , nilotinib , tyrosine kinase inhibitor , myeloid leukemia , cancer
Summary 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.