Nilotinib in Elderly Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) with Imatinib Resistance or Intolerance: Efficacy and Safety Analysis

Abstract Background: Nilotinib is a potent and highly selective BCR-ABL kinase inhibitor approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) patients in chronic (CML-CP) or accelerated phase (CML-AP) who have failed prior therapy including imatinib. Methods: This subanalysis of the open-label, single-arm, phase 2 study evaluated the efficacy and safety of nilotinib in elderly (≥65 years) CML-CP patients who were resistant or intolerant to imatinib. Nilotinib was dosed at 400 mg twice daily. Results: A total of 321 CML-CP patients (71% imatinib-resistant; 29% imatinib-intolerant) were enrolled. Thirty percent (98/321) of patients were ≥65 years; 8% (8/98) of these patients were 380 years. The baseline characteristics among patients ≥65 and <65 years were similar. Discontinuation of nilotinib due to adverse events was uncommon, and did not differ among the two age groups (18% in both groups). Efficacy was maintained in elderly patients, with 48% of patients achieving MCyR and 38% achieving CCyR, compared with 63% and 44% of patients <65 years achieving MCyR and CCyR, respectively. Duration of cytogenetic response was also consistent among age groups with 84% and 85% of responding elderly patients maintaining MCyR and CCyR at 18 months, compared with 85% and 89% of patients <65 years maintaining MCyR and CCyR at 18 months, respectively. Estimated overall survival (OS) rates at 12 months were 97% and 91%, for patients <65 years and ≥65 years, respectively. Overall, the safety profile of nilotinib was similar among the two age groups. Biochemical laboratory abnormalities were transient, clinically asymptomatic, and consistent in both age groups; elevated lipase occurred in 14% and 23%, and elevated total bilirubin occurred in 9% and 3% of patients <65 years and ≥65 years, respectively. The most common grade 3/4 hematological laboratory abnormalities were also comparable; neutropenia was reported in 31% and 30%, thrombocytopenia in 26% and 36%, and anemia in 8% and 15%, of patients <65 years or ≥65 years, respectively. The incidence of grade 3/4 pleural/pericardial effusions were <1% and 1% and grade 3/4 bleeding events were <1% and 1% in patients <65 years or ≥65 years, respectively. The incidence of myocardial infarction (<1% vs 4%), congestive heart failure (2% vs 1%), and QTcF prolongation >500 msec (<1% vs 2%) were also similar among patients <65 years or ≥65 years. Conclusions: Nilotinib is highly active and induced durable clinical responses in CML-CP patients regardless of age. Importantly, the safety profile of nilotinib is maintained in elderly patients and there was no increase in the incidence of cardiac evens making it an excellent therapeutic option for patients with Ph+ CML, regardless of age.

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