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Evaluation of Residual Disease and TKI Duration Are Critical Predictive Factors for Molecular Recurrence after Stopping Imatinib First-line in Chronic Phase CML Patients.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Nov 15; Vol. 25 (22), pp. 6606-6613. Date of Electronic Publication: 2019 Jul 10. - Publication Year :
- 2019
-
Abstract
- Purpose: Tyrosine kinase inhibitor (TKI) discontinuation is an emerging goal in chronic myelogenous leukemia (CML) management and several studies have demonstrated the feasibility of safely stopping imatinib. A sustained deep molecular response on long-term TKI is critical prior to attempting treatment-free remission. Reproducible results from several studies reported recently, failed to identify robust and reproducible predictive factors for the selection of the best candidates for successful TKI cessation.<br />Patients and Methods: We conducted a prospective national phase II study evaluating the cessation of imatinib after at least 2 years of MR4.5 obtained on imatinib first-line in patients with chronic phase CML.<br />Results: A total of 218 patients with de novo chronic phase CML were involved in the study. The median follow-up after imatinib cessation was 23.5 (1-64) months, 2 patients died from unrelated causes, and 107 experienced a confirmed increase in BCR-ABL1 levels defined as molecular recurrence. The molecular recurrence-free survival was 52% [95% confidence interval (CI), 45%-59%] at 6 months, and 50% (95% CI, 43%-57%) at 24 months. Droplet digital PCR (ddPCR) was used to evaluate more accurately low levels of BCR-ABL1 in 175 of 218 patients at imatinib cessation. To apply positive BCR-ABL1/ABL1 ratios on the international scale (IS), a conversion factor was calculated for ddPCR and the significant cut-off point was established at 0.0023% <superscript>IS</superscript> . In a multivariate analysis, the duration of TKI (≥74.8 months) and ddPCR (≥0.0023% <superscript>IS</superscript> ) were the two identified predictive factors of molecular recurrence, with P = 0.0366 (HR, 0.635; 95% CI, 0.415-0.972] and P = 0.008 (HR, 0.556; 95% CI, 0.360-0.858), respectively.<br />Conclusions: We conclude that the duration of TKI and residual leukemic cell load as determined by ddPCR are key factors for predicting successful treatment-free remission for patients with de novo chronic phase CML. See related commentary by Yan et al., p. 6561 .<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Adult
Aged
Drug Administration Schedule
Female
Fusion Proteins, bcr-abl genetics
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myeloid, Chronic-Phase genetics
Leukemia, Myeloid, Chronic-Phase pathology
Male
Middle Aged
Neoplasm Recurrence, Local
Prognosis
Prospective Studies
Remission Induction
Survival Analysis
Treatment Outcome
Imatinib Mesylate therapeutic use
Leukemia, Myeloid, Chronic-Phase drug therapy
Neoplasm, Residual diagnosis
Protein Kinase Inhibitors therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 25
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31292142
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-18-3373