Early Molecular Response and Female Sex Strongly Predict Achievement of Stable Undetectable BCR-ABL1, a Criterion for Imatinib Discontinuation in Patients with CML
| Autor: | David T Yeung, Jodi Prime, Brad Sullivan, Alexandra L. Yeoman, Susan Branford, Jasmina Georgievski, David M. Ross, Chani Field, Stuart Phillis, Timothy P. Hughes, Bronte A. Jamison, Haley Altamura |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Blood. 120:165-165 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v120.21.165.165 |
| Popis: | Abstract 165 Introduction. The opportunity to discontinue kinase inhibitor therapy while maintaining a deep remission is desirable for many CML patients. Despite good responses to imatinib for most patients, treatment related side effects remain problematic and can affect quality of life. Studies have demonstrated that a proportion of carefully selected patients can sustain response after imatinib discontinuation. The first requirement for successful discontinuation is likely to be stable deep molecular response based on a sensitive RQ-PCR assay. The criteria for patient selection in the French Stop Imatinib (STIM) and Australian CML8 (TWISTER) imatinib discontinuation trials included stable undetectable BCR-ABL1 transcripts for at least 24 months with a PCR sensitivity of 5 and 4.5 log, respectively. The probability of continued remission after discontinuation for imatinib treated patients without prior interferon-α therapy was approximately 33%. It is not known how many imatinib treated patients will eventually meet these PCR criteria for a discontinuation trial. Aims. We aimed to determine 1) the cumulative probability of achieving the PCR criteria for imatinib discontinuation as defined in the CML8 study, and 2) factors that predicted its achievement. Method. The molecular response of 415 de-novo CML patients in chronic phase enrolled in consecutive clinical trials of imatinib since July 2000 was examined. The assigned daily imatinib dose was 400 mg for 90 patients, 600 mg for 202 patients and 800 mg for 123 patients. Molecular data were included until imatinib cessation or last follow-up. The minimum time since commencing imatinib was 30 months and the median time on imatinib was 45 months, range 3 to 136. The CML8 PCR criteria for imatinib discontinuation were confirmed undetectable BCR-ABL1 transcripts at a sensitivity of 4.5 log that remained undetectable on all PCR tests for at least 24 months while on imatinib therapy. In the current analysis the CML8 PCR discontinuation criteria are defined as ‘stable UMR4.5'. Results. At 8 years of imatinib therapy the cumulative incidence of stable UMR4.5 was 43%, Figure A. Patients were divided into groups according to the time to a confirmed major molecular response (MMR): by 3, 6, 12 or 18 months. There was a significant difference in stable UMR4.5, P Conclusion. The time to achieve an MMR, sex and the 3 month BCR-ABL1 value predicted stable undetectable BCR-ABL1 while on imatinib. Lower BCR-ABL1 values and higher rates of stable UMR4.5 in females could be related to better drug adherence or biological differences. Further studies are indicated. Early MMR led to early achievement of the discontinuation criteria. The findings justify the focus on early achievement of MMR as a strategy to maximize recruitment to discontinuation studies. Disclosures: Branford: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cepheid: Consultancy. Ross:Novartis: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria. Yeung:Novartis Pharmaceuticals: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding. Hughes:Novartis, Bristol Myers-Squibb, and ARIAD: Honoraria, Research Funding. |
| Databáze: | OpenAIRE |
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