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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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
François-Xavier
FX
Laboratoire d'Hématologie et Service des Maladies du Sang, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. francois-xavier.mahon@umr5540.u-bordeaux2.fr
Réa
Delphine
D
Guilhot
Joëlle
J
Guilhot
François
F
Huguet
Françoise
F
Nicolini
Franck
F
Legros
Laurence
L
Charbonnier
Aude
A
Guerci
Agnès
A
Varet
Bruno
B
Etienne
Gabriel
G
Reiffers
Josy
J
Rousselot
Philippe
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D053208:Kaplan-Meier Estimate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000235:genetics; D011743:Pyrimidines / Q000008:administration & dosage*; D012008:Recurrence; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C406060:abl-bcr fusion protein, human; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl