ABCB1 mRNA overexpression may predict patients with chronic myeloid leukemia (CML) likely to be resistant to first- and second-generation tyrosine kinase inhibitors (TKIs) and who may derive greater benefit from alternative treatment strategies, a study published in Leukemia has shown.1
TKI therapy induces excellent response rates in the majority of patients with CML. Although first-line treatment with imatinib, with selective switching to nilotinib in patients resistant or intolerant to imatinib, improves survival and molecular responses, imatinib is less effective in patients with primary resistance to this TKI.
Further, 25% of patients develop secondary resistance, leading to treatment failure in approximately 20% to 35% of those initially treated with imatinib.
Therefore, researchers sought to identify biomarkers to identify patients who might develop resistance to TKIs. Because the drug efflux transporter ABCB1 has been thought to play a role in TKI resistance, the investigators assessed whether early increases in ABCB1 mRNA expression predict for patient response.
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Results showed that patients exhibiting ABCB1 mRNA overexpression were significantly less likely to achieve an early molecular response at 3 months (P = .001), a major molecular response (P < .0001), and a deep molecular response (P < .0001).
These patients also had a lower likelihood of achieving a major molecular response when switched to nilotinib.
- Eadie LN, Dang P, Saunders VA, et al. The clinical significance of ABCB1 overexpression in predicting outcome of CML patients undergoing first-line imatinib treatment. Leukemia. 2016 Jul 15. doi: 10.1038/leu.2016.179. [Epub ahead of print]