Characteristics of Patients with Chronic Myelogenous Leukemia in Chronic Phase Switched to Nilotinib or Dasatinib As Second-Line Therapy

Abstract

AbstractAbstract 4447 Background:Since 2007, nilotinib and dasatinib have been available for 2nd-line therapy for patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. In clinical trials, both drugs have been shown to be effective and safe, but with different side-effect profiles. Currently, little is known about the characteristics of patients who are switched to nilotinib or dasatinib in a real-world setting. Methods:Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to either 2nd-line nilotinib or dasatinib and who had at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients from each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information on patient characteristics at the time of switching TKI therapy was collected, including age, sex, race, comorbidities, prior imatinib dosing, reasons for switching, and the dose regimen of nilotinib or dasatinib at initiation. Characteristics were compared between nilotinib and dasatinib patients using Wilcoxon and chi-square tests. Results:122 hematologists and oncologists provided information on 597 patients (301 on 2nd-line nilotinib and 296 on 2nd-line dasatinib). The table below summarizes the comparisons of the two groups. Both groups had similar age, sex, race, and comorbidity profile. Nilotinib patients were more likely than dasatinib patients to have had secondary imatinib resistance (p=0.047), more likely to have received a maximum imatinib dosing of 600 or 800 mg/day (p=0.006), and less likely to have switched due to imatinib intolerance (p=0.024). Conclusions:Patients switched to nilotinib vs. dasatinib had similar demographic and clinical characteristics at the time of switch, but nilotinib patients were more likely to have had an imatinib dose increase before the switch, and were more likely to have had secondary imatinib resistance. Patients switched to nilotinib vs. dasatinib were also less likely to have had imatinib intolerance. These findings suggest that resistance or intolerance to imatinib therapy have had more impact than patient demographics or clinical characteristics in deciding which drug to use for 2nd-line therapy.Patient characteristicsNilotinibDasatinibP-value(n=301)(n=296)Median age, years (range)60 (22, 83)60 (21, 83)0.431Male n (%)202 (67.1)189 (63.9)0.402Race, n (%)American Indian or Alaska Native7 (2.3)6 (2.0)0.803Asian16 (5.3)24 (8.1)0.172Black or African American42 (14.0)47 (15.9)0.509Hispanic or Latino26 (8.6)15 (5.1)0.085Native Hawaiian or Other Pacific Islander6 (2.0)4 (1.4)0.541White203 (67.4)201 (67.9)0.904Median CML duration, months (range)15 (1,101)13 (1,100)0.110Selected comorbidities, n (%)CML only166 (55.1)159 (53.7)0.725Cardiovascular disease including myocardial infarction, congestive heart failure and peripheral vascular disease42 (14.0)37 (12.5)0.600Dementia4 (1.3)8 (2.7)0.232Chronic pulmonary disease44 (14.6)35 (11.8)0.314Connective tissue disease5 (1.7)10 (3.4)0.180Peptic ulcer disease25 (8.3)30 (10.1)0.440Moderate or severe renal disease7 (2.3)5 (1.7)0.580Cerebrovascular disease with mild or no residual TIA3 (1.0)3 (1.0)0.984Liver disease12 (4.0)17 (5.7)0.318Diabetes36 (12.0)32 (10.8)0.659Other6 (2.0)13 (4.4)0.095Highest imatinib dose, n (%)<400 mg/day154 (51.2)183 (61.8)0.006401-600 mg/day81 (26.9)69 (23.3)601-800 mg/day66 (21.9)44 (14.9)Reason for the switch to a second-line TKI, n (%)Primary imatinib resistance122 (40.5)116 (39.2)0.738Secondary imatinib resistance105 (34.9)81 (27.4)0.047Adverse events or intolerance of imatinib67 (22.3)90 (30.4)0.024Patient not adherent to imatinib3 (1.0)6 (2.0)0.302Other[1]4 (1.3)3 (1.0)0.720[1]Notes: [1] Other reasons for switching from nilotinib included ‘patient's request’ (2), ‘recurrent disease', and ‘data suggest improved efficacy'; from dasatinib, ‘high Sokal score', ‘suboptimal cytogenetic response' and ‘patient compliance'. Disclosures:Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Griffin:Novartis: Consultancy, Research Funding.