Evaluating the impact of a switch to nilotinib on imatinib-related chronic low-grade adverse events in patients with CML-CP: the ENRICH study

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2016-05, Vol.16 (5), p.286-296
• Main Authors: Cortes, Jorge E., MD, Lipton, Jeffrey H., FRCPC, MD, PhD, Miller, Carole B., MD, Busque, Lambert, MD, Akard, Luke P., MD, Pinilla-Ibarz, Javier, MD, PhD, Keir, Christopher, MD, MS, Warsi, Ghulam, PhD, Lin, Felice P., PharmD, Mauro, Michael J., MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Chronic myeloid leukemia; Clinical trials; Drug Substitution; Female; Hematology, Oncology and Palliative Medicine; Humans; Imatinib Mesylate - adverse effects; Imatinib Mesylate - therapeutic use; Imatinib-related chronic adverse events; Leukemia, Myeloid, Chronic-Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - genetics; Male; Middle Aged; Nilotinib; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - therapeutic use; Quality of Life; Switch; Treatment Outcome
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2016.02.002

Abstract Background Many patients with chronic myeloid leukemia in chronic phase (CML-CP) experience chronic treatment-related adverse events (AEs) on imatinib therapy. These AEs can impair quality of life (QOL) and lead to reduced treatment adherence, which is associated with poor clinical outcomes. Patients and Methods In the phase 2 Exploring Nilotinib to Reduce Imatinib Related Chronic Adverse Events (ENRICH) study (N = 52), the impact 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 patients had overall improvement in imatinib-related AEs (primary endpoint). Of 210 imatinib-related AEs identified at baseline, 62.9% resolved within 3 months of switching to nilotinib. Among evaluable patients, most had improvements in overall QOL after switching to nilotinib. At screening, 65.4% of evaluable patients had a major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale). After switching to nilotinib, the rate of MMR was 76.1% at 3 months and 87.8% at 12 months. Treatment-emergent AEs reported on nilotinib were typically grade 1/2; however, some patients developed more serious AEs, and 8 patients discontinued nilotinib due to new or worsening AEs. Conclusions Overall, results from ENRICH demonstrated that switching to nilotinib can mitigate imatinib-related chronic low-grade nonhematologic AEs in patients with CML-CP in conjunction with acceptable safety and achievement of molecular responses. This trial was registered at www.clinicaltrials.gov as NCT00980018.