Abstract
Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR 4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR 4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR 4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR 4, and MR 4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.
Highlights
Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder caused by a reciprocal balanced translocation between the ABL1 locus and the BCR regions in the long arms of chromosome 9 and 22, respectively, which results in the formation of the BCR-ABL1 fusion gene
Based on the promising results of the landmark phase 3 trial, along with risks of adverse events (AEs) comparable with imatinib, its use was approved for the treatment of newly diagnosed CML in chronic phase (CML-CP) and imatinib-resistant or imatinib- intolerant CML in chronic or accelerated phase [4]
We report the results of Evaluating Nilotinib Efficacy and Safety in Clinical Trials- Korea (ENESTKorea) which evaluated the 2-year efficacy and safety of nilotinib treatment, and the relationship between the plasma nilotinib concentration (PNC) and clinical outcomes using prospectively collected patient data and plasma samples of CML-CP patients treated with nilotinib in South Korea
Summary
Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder caused by a reciprocal balanced translocation between the ABL1 locus and the BCR regions in the long arms of chromosome 9 and 22, respectively, which results in the formation of the BCR-ABL1 fusion gene. Based on the promising results of the landmark phase 3 trial, along with risks of adverse events (AEs) comparable with imatinib, its use was approved for the treatment of newly diagnosed CML in chronic phase (CML-CP) and imatinib-resistant or imatinib- intolerant CML in chronic or accelerated phase [4]. Even with this highly effective agent, there are still many patients for whom the therapeutic response is inadequate, or toxicity is limiting the treatment [7]. There is room for further optimization of the current CML therapy
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