Evaluating the Impact of a Switch to Nilotinib on Imatinib-Related Chronic Low-Grade Adverse Events in Patients With CML-CP: The ENRICH Study

Abstract

Background: Many patients with chronic myeloid leukemia in chronic phase experience chronic treatment-related adverse events (AEs) during imatinib therapy. These AEs can impair quality of life and lead to reduced treatment adherence, which is associated with poor clinical outcomes.

Patients and methods: In the phase II ENRICH (Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events) study (N = 52), the effect of switching patients with imatinib-related chronic low-grade nonhematologic AEs from imatinib to nilotinib was evaluated.

Results: Three months after switching to nilotinib, 84.6% of the patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% had resolved within 3 months of switching to nilotinib. Of evaluable patients, most had improvements in overall quality of life after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of the major molecular response was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported with nilotinib were typically grade 1 or 2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib because of new or worsening AEs.

Conclusion: Overall, results from the ENRICH study demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with chronic myeloid leukemia in chronic phase, in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018.

Keywords: Chronic myeloid leukemia; Clinical trials; Imatinib-related chronic adverse events; Nilotinib; Switch.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Effects on Imatinib-Related Chronic Low-Grade Nonhematologic AEs

A) Change in status of imatinib-related AEs at EOC 1 and EOC 3 relative to baseline (percentages were derived from the 210 total imatinib-related AEs reported at baseline). B and C) Proportion of imatinib-related AEs that were improved at (B) EOC 1 and (C) EOC 12 for each patient. AE, adverse event; EOC, end of cycle.

Figure 2. Molecular Response After Switch to Nilotinib (N = 52)

Rates of MMR, MR4, and MR4.5 were calculated among evaluable patients at each time point. EOC, end of cycle; MMR, BCR-ABL1IS ≤ 0.1%; MR4, BCR-ABL1IS ≤ 0.01%; MR4.5, BCR-ABL1IS ≤ 0.0032%. Of the 52 patients, 15 did not have results for ≥ 1 time point shown.

Figure 3. Change in Overall QOL

For each time point, the proportion of patients reporting better, unchanged, or worse QOL relative to baseline was calculated based on the total patient population (N = 52). QOL was evaluated at each time point for (A) the prior 24 hours and (B) the prior 7 days. EOC, end of cycle; QOL, quality of life.

Figure 4. Mean Change in MDASI-CML Scores

For each time point, the mean change in MDASI-CML specific symptom and MDASI-CML interference item scores relative to baseline were calculated among evaluable patients. A decrease in MDASI-CML score indicates improvement. EOC, end of cycle; MDASI-CML, MD Anderson Symptom Inventory-Chronic Myeloid Leukemia.