title: Early molecular response and female sex strongly predict stable undetectable BCR-ABL1, the criteria for imatinib discontinuation in patients with CML.
abstract: Recent studies have demonstrated that some patients with chronic myeloid leukemia (CML) can maintain remission after discontinuation of imatinib. A prerequisite is stable, undetectable BCR-ABL1. It is not known how many patients achieve this response or the factors associated with its achievement. We examined 423 de novo imatinib-treated patients to determine the cumulative incidence of achieving the discontinuation criteria as defined in the CML8 study (≥2 years of undetectable BCR-ABL1 [Stable MR(4.5)]), and predictive factors. After 8 years of imatinib, the cumulative incidence of Stable MR(4.5) was 36.5%. Therefore, 9% to 15% of first-line imatinib-treated patients would maintain remission after discontinuation. The BCR-ABL1 level at 3 months and factors at diagnosis were examined for association with Stable MR(4.5): Sokal risk, age, sex, and assigned imatinib dose. The only independent predictors were female sex (54.4% vs 27.2%; P = .018) and the 3-month BCR-ABL1 (P < .001). The highest cumulative incidence of Stable MR(4.5) after 8 years was 78.2% for patients with BCR-ABL1 ≤ 0.10%(IS) at 3 months (n = 38). Time to major molecular response (MMR) influenced the time to reach Stable MR(4.5) (P < .001), suggesting slower dynamics of response with a delayed MMR. The findings justify the focus on rapid reduction of BCR-ABL1 as a strategy to maximize potential suitability for imatinib discontinuation studies. The Iris trial was registered at http://www.clinicaltrials.gov as NCT00006343. The Tops trial was registered at http://www.clinicaltrials.gov as NCT00124748. The TIDEL I trial was registered at www.ANZCTR.org.au as ACTRN12607000614493. The TIDEL II trial was registered at www.ANZCTR.org.au as ACTRN12607000325404.
authors.affiliation: Department of Genetics and Molecular Pathology, Centre for Cancer Biology, SA Pathology, Adelaide, Australia. susan.branford@health.sa.gov.au
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: David T
authors.initials: DT
authors.lastname: Yeung
authors.forename: David M
authors.initials: DM
authors.lastname: Ross
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Prime
authors.forename: Chani R
authors.initials: CR
authors.lastname: Field
authors.forename: Haley K
authors.initials: HK
authors.lastname: Altamura
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Yeoman
authors.forename: Jasmina
authors.initials: J
authors.lastname: Georgievski
authors.forename: Bronte A
authors.initials: BA
authors.lastname: Jamison
authors.forename: Stuart
authors.initials: S
authors.lastname: Phillis
authors.forename: Brad
authors.initials: B
authors.lastname: Sullivan
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Briggs
authors.forename: Mark
authors.initials: M
authors.lastname: Hertzberg
authors.forename: John F
authors.initials: JF
authors.lastname: Seymour
authors.forename: John
authors.initials: J
authors.lastname: Reynolds
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis / Q000378:metabolism; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D020732:Cytogenetic Analysis; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis* / Q000097:blood / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D012074:Remission Induction; D012737:Sex Factors; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D054316:Biomarkers, Pharmacological; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl