Chronic Myeloid Leukemia: Overview of New Agents and Comparative Analysis

Discovery of targeted BCR-ABL protein tyrosine kinase inhibitors (TKI) in the therapy of patients with chronic myeloid leukemia (CML) is perhaps the most popular success story in oncology. Imatinib is the most common TKI modality used as a frontline therapy in CML across the world. Lately, randomized control trials have shown that second-generation TKI, such as dasatinib and nilotinib, are superior to imatinib in terms of tolerability and efficacy. Therefore, second-generation TKI have been used increasingly as a first choice for patients with CML in chronic phase (CML-CP). Recently, ponatinib has shown significant efficacy against the most resistant cases (including those with T315I mutations) with CML. Omacetaxine is a non-TKI agent with a different mechanism of action and has shown benefit in resistant CML. Analysis of other novel agents and newer mechanisms affecting CML stem cells are under exploration. With these developments, the life expectancy of the majority of patients (> 90 %) with CML-CP has become comparable to a healthy age-matched individual. The focus has now shifted to achieving faster and deeper responses, considering these parameters as a surrogate for long-term outcome and possibly cures in patients with CML. Adherence to therapy with TKI, proper monitoring by standardized techniques, and adequate use of the available therapies are established rules of managing patients with CML. However, even with these advances, problems of drug resistance, loss of response, kinase domain mutations, transformations in CML (accelerated and blast phase), and patient noncompliance prevail in the community practice. Early identification of resistant cases, feasibility for allogeneic stem cell transplantation (allo-SCT), and enrollment in clinical trials with newer drugs is warranted. This article compares the efficacy and safety results of various TKI and non-TKI modalities and other novel pharmacological agents in the therapy of CML.