Join Guillermo Garcia-Manero, MD and Elias Jabbour, MD as they present their multidisciplinary expertise on a range of cases pertaining to chronic myelogenous leukemia.

CML is characterized by the presence of Ph chromosome resulting from the translocation between chromosomes 9 and 22.  TKI therapy with small molecule BCR-ABL inhibitors (imatinib, nilotinib or dasatinib) has become the standard of care for patients with newly diagnosed chronic phase CML based on their successful induction of durable responses in the vast majority of patients. Recent studies have suggested that achievement of cytogenetic and molecular response at 3 months following first-line TKI therapy is an important prognostic indicator for durable responses and long-term survival. While dasatinib and nilotinib are active against most of the imatinib resistant BCR-ABL kinase domain mutations, available evidence supports the emergence of other BCR-ABL mutations resistant to dasatinib and nilotinib. In addition, all of the currently approved TKIs are resistant to T315I mutation. Omacetaxine, bosutinib and ponatinib have shown promising results in the management of patients with T315I and other BCR‑ABL mutations resistant to imatinib, dasatinib and nilotinib.

The goal of therapy for patients with chronic phase CML is to prevent disease progression by the achievement adequate cytogenetic and molecular responses at specific time points. Monitoring response to TKI therapy with quantitative PCR using international scale and bone marrow cytogenetics is crucial to identify the subgroup of patients who would benefit from early intervention with alternate treatment options.Mutational analysis at the time of failure with imatinib, dasatinib, or nilotinib is essential to select the optimal second-line TKI therapy in patients with identifiable mutations. Discontinuation of TKI therapy (with close molecular monitoring) may be possible in selected patients with sustained complete molecular response. However, at the present time, the NCCN Guidelines recommend TKI therapy indefinitely in responding patients. Adequate and appropriate management of side effects is an integral part of clinical management to improve patient adherence to TKI therapy.

For patients with CML, clinicians need to be aware of comorbidities, response to therapy, potential drug interactions, the presence of mutations, and any toxicity to therapy. The goal of therapy for patients with chronic phase CML is to prevent disease progression by the achievement adequate cytogenetic and molecular responses at specific time points. Monitoring response to TKI therapy with quantitative PCR using international scale and bone marrow cytogenetics is crucial to identify the subgroup of patients who would benefit from early intervention with alternate treatment options. Adequate and appropriate management of side effects is an integral part of clinical management to improve patient adherence to TKI therapy.