Speculative model of future clinical Abl kinase inhibitor treatment options for CML. Imatinib responses are well-established (purple trace). Durable responses are the rule in early chronic phase but the exception in blast crisis.1,6,7 Responses to second-line inhibitors (dasatinib11,38,39,50 and nilotinib10,41 ) are based on limited preliminary evidence (green trace). We speculate that a slightly larger proportion of patients with AP/BC may achieve a sustained response, but this remains to be determined. Abl kinase inhibitor cocktails that include a 315T>I inhibitor (orange trace) and cover all kinase domain mutants have not been used in the clinic. The hypothetical curve shown represents what may be achievable with Bcr-Abl kinase–directed therapy. Patients who have had relapse with partially or fully Bcr-Abl–independent disease are the most enigmatic population in terms of forecasting responses. This speculative model is most applicable to patients with Bcr-Abl–dependent disease.
