How I treat newly diagnosed chronic phase CML

Abstract

The progress made in the understanding of chronic myeloid leukemia (CML) since the recognition of a common chromosomal abnormality to the introduction of ever more effective tyrosine kinase inhibitors is unprecedented in cancer. The expected survival for patients diagnosed with CML today, if properly managed, is probably similar to that of the general population. When managing patients with CML the goal is to achieve the best longterm outcome and we should base the treatment decisions on the data available. The results from cytogenetic and molecular analyses have to be interpreted judiciously and all available treatment options integrated into the treatment plan properly. The availability of several treatment options in CML is an asset, but the temptation of rapid succession of treatment changes because of perceived suboptimal response or for adverse events that could be managed needs to be avoided. Any decision to change therapy needs to weigh the expected long-term outcome with the current option versus the true expectations with any new option, particularly as it relates to irreversible outcomes, such as transformation to blast phase and death. In this manuscript, we discuss the treatment approach that has helped us manage successfully a large CML population. (Blood. 2012;120(7):1390-1397)

Assessment of Interleukin 1β Serum Level in Different Responder Groups and Stages of Chronic Myeloid Leukemia Patients on Imatinb Mesylate Therapy

“…The progress made in the understanding of chronic myeloid leukemia since the recognition of a common chromosomal abnormality to the introduction of evermore effective tyrosine kinase inhibitors is unprecedented in cancer [19]. Recent mathematical models have been developed to study the dynamics of CML under imatinib treatment.…”

Excellent therapeutic results achieved in chronic myeloid leukemia patients with front‐line imatinib and early treatment modifications in suboptimal responders: A retrospective study on 91 unselected patients

“…In phase III studies comparing second generation TKI to standard imatinib treatment, a lower proportion of patients progressing to the accelerated/blastic phase was observed with second generation TKI compared to imatinib treatment; however, that difference reached a statistically significance with nilotinib but not with dasatinib or bosutinib therapy [16][17][18][19]. Dasatinib and nilotinib have been approved, both in Europe and USA, for first-line CML treatment and are claimed by some authors to represent now the standard front-line CML therapy [20], in spite of their higher costs and some uncertainty on their long-term side effects [21][22][23][24][25][26][27], compared to imatinib.…”

FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance

“…In CML, the current practice is to change TKIs when new mutations are recognized in a patient. Similarly, in FLT3-mutated AML, the varying resistance patterns of different inhibitors may give rise to a situation where either switching of therapy is necessitated by acquired mutations or combinations of therapy are necessary to avoid development of resistance [53].…”

“…The efficacy of crenolanib as a FLT3 TKI is currently being investigated in two phase 2 clinical trials of AML patients, one of which is specifically enrolling patients that have progressed on prior FLT3 TKI therapy. Now that agents are arising that have activity against the TKD mutation, the model for FLT3/ITD AML is beginning to approximate the CML model, where specific resistanceconferring mutations arise during therapy with one TKI, necessitating a change to a different inhibitor [53].…”