Association of early molecular response to nilotinib with probability of cytogenetic response in chronic myeloid leukemia patients (pts) who fail imatinib
Date
2010
Authors
Branford, S.
Martinelli, G.
Saglio, G.
Kim, D.
Shou, Y.
Reynolds, J.
Woodman, R.
Kantarjian, H.
Hochhaus, A.
Radich, J.
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Conference paper
Citation
Journal of Clinical Oncology, 2010; 28(15 Suppl):6513
Statement of Responsibility
S. Branford, G. Martinelli, G. Saglio, D. Kim, Y. Shou, J. Reynolds, R. C. Woodman, H. Kantarjian, A. Hochhaus and J. P. Radich
Conference Name
American Society of Clinical Oncology Annual Meeting (2010 : Chicago, Ill.)
Abstract
Background: Response dynamics in pts treated with nilotinib for imatinib failure may be different than imatinib in front line. Many pts treated with nilotinib in the second line achieved cytogenetic responses early (median time to MCyR and CCyR of 2.8 mo and 3.3 mo). A previous landmark analysis demonstrated BCR-ABL% (IS) at 3 months (mo) on nilotinib predicted achievement of subsequent cytogenetic response. Here, we investigated whether early molecular response before 3 mo was associated with subsequent cytogenetic response. Methods: CML-CP pts (N = 321) with imatinib resistance or intolerance were grouped by 1 mo BCR-ABL% (IS) and landmark analyses were performed to evaluate probability of cytogenetic response with a minimum follow-up of 24 mo. Results: Early molecular response of BCR-ABL% (IS) ≤ 10 occurred in 19% of pts who received nilotinib. Pts with BCR-ABL% (IS) >1 – ≤10 (n = 37) had higher probability of MCyR by 12 mo (84%) compared with pts with BCR-ABL% (IS) >10 (55%) (n = 202). Pts with BCR-ABL% (IS) >1 – ≤10 also had higher probability of achieving CCyR by 12 mo (72%) compared with pts with BCR-ABL% (IS) >10 (38%). Similar trends in the probability of achieving MCyR and CCyR on nilotinib by 12 mo were observed for pts when analyzed by the presence or absence of baseline (BL) mutations (Table). Similar results were seen when analyzing the probability of cytogenetic response by 24 mo. Estimated MCyR and CCyR by 12 mo by BCR-ABL% (IS) at 1 mo on nilotinib therap. Conclusions: Molecular response to nilotinib at 1 mo was associated with cytogenetic responses by 12 and 24 mo, even in the presence of BL mutations. While treatment decisions based on 1 mo BCR-ABL% (IS) are not recommended, these data indicate that reductions in BCR-ABL transcripts may occur before 3 mo on nilotinib and are associated with subsequent cytogenetic responses in these pts.
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© 2010 American Society of Clinical Oncology