Laura N Eadie
South Australian Health and Medical Research Institute, Australia
Posters & Accepted Abstracts: Immunother Open Acc
Background & Aims: The TIDEL II trial indicates first-line imatinib treatment with selective switching to nilotinib for failure to meet specific molecular targets/intolerance, results in excellent molecular responses and overall survival. Drug transporters, particularly OCT-1 and ABCB1, impact imatinib response. Here, the clinical significance of ABCB1 overexpression in response to imatinib therapy was assessed in patients enrolled to TIDEL II. Method: ABCB1 mRNA expression was assessed by PCR at day 0, day 22 post imatinib therapy initiation and, where relevant, at cessation in CP-CML patients. Results: A change in ABCB1 expression after 22 days of imatinib (compared with baseline) was observed (range 0.6-2.3 fold, median 2-fold), suggesting imatinib may alter ABCB1 expression. This change was not related to BCR-ABL1 expression (p=0.29 at day 0 and p=0.84 at day 28). When patients with a ΓΆΒ?Β¥2-fold rise in ABCB1 expression were compared with those with a <2-fold rise significant differences in outcome were revealed. Nilotinib is also exported by ABCB1; accordingly, patients with ΓΆΒ?Β¥2-fold rise in ABCB1 were less likely to achieve MMR when switched to nilotinib therapy (11% vs. 70% of patients with <2-fold rise). Conclusion: This rapid PCR-based assay performed pre and 22 days-post imatinib initiation provides a potent early predictor of subsequent imatinib response in CP-CML patients; these data also suggest nilotinib is a poor therapeutic option for patients with upregulated ABCB1 expression in response to imatinib. Results shown here exemplify how drug transporters can influence TKI therapy and patient response and provide a new, effective and easily translatable prognostic biomarker based on ABCB1 expression.
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