A Disease Model to Predict the Long-Term Outcomes Associated with Treatments for Chronic Myelogenous Leukemia (CML).

Dasatinib, a BCR-ABL inhibitor 325 fold more potent than imatinib, has been studied in DASISION a randomized comparison vs. imatinib in patients with newly diagnosed chronic phase CML. A computer simulation disease model was developed to examine long-term survival outcomes following treatment with dasatinib, imatinib, or nilotinib in this patient population.

A disease model was developed to estimate the lifetime health outcomes associated with each form of treatment. Five initial best-response categories were used (no response (NR), complete hematologic response (CHR), partial cytogenetic response (PCyR), complete cytogenetic response (CCyR) and molecular response (MR)), which were each linked to a disease prognosis based on previously published evidence. Mutually exclusive initial response rates for NR, CHR, PCyR, CCyR and MR came from the DASISION trial for dasatinib and imatinib while those for nilotinib were identified from published ENESTnd data. A quality of life (QoL) utility value was assigned to each health state (chronic phase with response, chronic phase without response, progressed, and dead), also from previous publications. Adverse events were accounted for in terms of their impact upon QoL utility values. Extrapolation beyond the published data was undertaken by calculating trend rates for the final three years of follow up and applying age related mortality rates. Uncertainty was incorporated into the analysis by fitting distributions to survival and using simulation techniques to run 1,000 iterations. The model calculated survival based on the mean number of years’ survival per patient, across the entire cohort. Adjusted QoL utility values were calculated by assigning a QoL utility value weight to each state (see above) and calculating the mean total outcome for the entire cohort. Incremental survival was calculated by comparing the mean survival associated with each treatment.

The quality adjusted life years (QALYs) and life years (LYs) are given in Table 1. The QALYs and LYs were 12.238 and 14.727 for dasatinib, 11.506 and 13.822 for imatinib and 12.016 and 14.426 for nilotinib, respectively.

Based on simulation modeling, results suggest that treatment with dasatinib may be associated with long-term survival as well as QoL-adjusted survival benefits. Long-term follow-up of ongoing studies will be needed to confirm these predicted benefits.

Taylor:Bristol Myers-Squibb: Consultancy. Lewis:Bristol Myers-Squibb: Consultancy. Patton:Bristol Myers-Squibb: Consultancy. Hirji:Bristol Myers-Squibb: Employment. Davis:Bristol Myers-Squibb: Employment.