12th Congress of the European Hematology ... - Haematologica

from pivotal clinical trials. Methods. Adverse event (AE) data were
extracted for patients who had at least two occurrences of daily imatinib
dose escalated from 400 mg to 600 or 800 mg from the 5-year IRIS study
in newly diagnosed CP-CML patients (N=158) and, for those receiving
dasatinib 70 mg twice daily for imatinib-resistant or intolerant CP-CML,
from the FDA’s publicly-available Sprycel Drug Approval Package
(N=186 to 214). AEs were selected based on their frequency, clinical significance
and availability. Conservative approaches to systematically
favor dasatinib were employed throughout the analysis. Incidence rates
were reported as number of patients with the AE per 100 patient-years
of observation, and incidence rate ratios were used to compare both
drugs using Poisson distribution. The imatinib group’s observation period
was constructed based on time periods of imatinib treatment beginning
from the date of dose escalation to > 400 mg, and ending at the earliest
of the last imatinib treatment date or the AE end date, thus assuming
AE occurrence even during treatment gaps. For the dasatinib group,
in the absence of specific patient-level data, it was conservatively
assumed that all AEs occurred only at the latest treatment end date
(279th day) for the group, artificially increasing the denominator for the
incidence rate calculation which in turn underestimated the AE incidence
for the dasatinib group. All AEs (drug-related or not) were considered
for imatinib, whereas only those judged by the investigator as drugrelated
were included for dasatinib. Sensitivity analyses based on the
subset of HD imatinib patients receiving ? 800 mg or the HD imatinib
patients receiving interferon-alfa plus cytarabine before crossing over to
standard imatinib dose were also conducted. Results. At baseline, relative
to HD imatinib, the dasatinib group was older (mean age; 56.5 vs. 49.5
years, p