Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial.

Imatinib treatment significantly improves survival in patients with chronic myeloid leukaemia (CML), but little is known about whether treatment can safely be discontinued in the long term. We aimed to assess whether imatinib can be discontinued without occurrence of molecular relapse in patients in complete molecular remission (CMR) while on imatinib. In our prospective, multicentre, non-randomised Stop Imatinib (STIM) study, imatinib treatment (of >2 years duration) was discontinued in patients with CML who were aged 18 years and older and in CMR (>5-log reduction in BCR-ABL and ABL levels and undetectable transcripts on quantitative RT-PCR). Patients who had undergone immunomodulatory treatment (apart from interferon α), treatment for other malignancies, or allogeneic haemopoietic stem-cell transplantation were not included. Patients were enrolled at 19 participating institutions in France. In this interim analysis, rate of relapse was assessed by use of RT-PCR for patients with at least 12 months of follow-up. Imatinib was reintroduced in patients who had molecular relapse. This study is registered with ClinicalTrials.gov, number NCT00478985. 100 patients were enrolled between July 9, 2007, and Dec 17, 2009. Median follow-up was 17 months (range 1-30), and 69 patients had at least 12 months follow-up (median 24 months, range 13-30). 42 (61%) of these 69 patients relapsed (40 before 6 months, one patient at month 7, and one at month 19). At 12 months, the probability of persistent CMR for these 69 patients was 41% (95% CI 29-52). All patients who relapsed responded to reintroduction of imatinib: 16 of the 42 patients who relapsed showed decreases in their BCR-ABL levels, and 26 achieved CMR that was sustained after imatinib rechallenge. Imatinib can be safely discontinued in patients with a CMR of at least 2 years duration. Imatinib discontinuation in this setting yields promising results for molecular relapse-free survival, raising the possibility that, at least in some patients, CML might be cured with tyrosine kinase inhibitors.

Mahon FX ，Réa D ，Guilhot J ，Guilhot F ，Huguet F ，Nicolini F ，Legros L ，Charbonnier A ，Guerci A ，Varet B ，Etienne G ，Reiffers J ，Rousselot P ，Intergroupe Français des Leucémies Myéloïdes Chroniques ... -  《-》

Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease.

Rousselot P ，Charbonnier A ，Cony-Makhoul P ，Agape P ，Nicolini FE ，Varet B ，Gardembas M ，Etienne G ，Réa D ，Roy L ，Escoffre-Barbe M ，Guerci-Bresler A ，Tulliez M ，Prost S ，Spentchian M ，Cayuela JM ，Reiffers J ，Chomel JC ，Turhan A ，Guilhot J ，Guilhot F ，Mahon FX ... -  《-》

Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission.

Paschka P ，Müller MC ，Merx K ，Kreil S ，Schoch C ，Lahaye T ，Weisser A ，Petzold A ，König H ，Berger U ，Gschaidmeier H ，Hehlmann R ，Hochhaus A ... -  《LEUKEMIA》

Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR.

Ross DM ，Branford S ，Seymour JF ，Schwarer AP ，Arthur C ，Bartley PA ，Slader C ，Field C ，Dang P ，Filshie RJ ，Mills AK ，Grigg AP ，Melo JV ，Hughes TP ... -  《-》

Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate.

Cortes J ，Talpaz M ，O'Brien S ，Jones D ，Luthra R ，Shan J ，Giles F ，Faderl S ，Verstovsek S ，Garcia-Manero G ，Rios MB ，Kantarjian H ... -  《CLINICAL CANCER RESEARCH》