title: Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study.
abstract: Most patients with chronic myeloid leukemia (CML) treated with imatinib will relapse if treatment is withdrawn. We conducted a prospective clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease (UMRD) by conventional quantitative polymerase chain reaction (PCR) on imatinib for at least 2 years. Patients stopped imatinib and were monitored frequently for molecular relapse. At 24 months, the actuarial estimate of stable treatment-free remission was 47.1%. Most relapses occurred within 4 months of stopping imatinib, and no relapses beyond 27 months were seen. In the 21 patients treated with interferon before imatinib, a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk, as was slower achievement of UMRD after switching to imatinib. Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD, even several years after imatinib withdrawal. No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations (median follow-up, 42 months). All patients who relapsed remained sensitive to imatinib re-treatment. These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent, sensitive molecular monitoring and early rescue of molecular relapse.
authors.affiliation: Haematology, SA Pathology, Adelaide, Australia. david.ross@health.sa.gov.au
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: Christopher
authors.initials: C
authors.lastname: Arthur
authors.forename: David T
authors.initials: DT
authors.lastname: Yeung
authors.forename: Phuong
authors.initials: P
authors.lastname: Dang
authors.forename: Jarrad M
authors.initials: JM
authors.lastname: Goyne
authors.forename: Cassandra
authors.initials: C
authors.lastname: Slader
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Filshie
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Mills
authors.forename: Junia V
authors.initials: JV
authors.lastname: Melo
authors.forename: Deborah L
authors.initials: DL
authors.lastname: White
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Grigg
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate