Are there better Bcr-Abl kinase inhibitors for chronic myeloid leukaemia than imatinib?

Abstract

The Bcr-Abl kinase inhibitor imatinib is the standard treatment for chronic myeloid leukaemia (CML). Some subjects with CML do not respond to, or are intolerant of, imatinib. Nilotinib and dasatinib were initially developed to treat these subjects, and were shown to be effective. They are now being trialled as initial 'inib' treatment for CML. The objective was to evaluate the recent Phase III clinical trials comparing nilotinib or dasatinib with imatinib in newly diagnosed CML. Nilotinib and dasatinib were shown to give a higher rate of complete cytogenic and major molecular responses than imatinib over 1 year. They should be considered as first choice in the treatment of subjects who develop CML. However, there are still major limitations to the populations with which these 'inib' drugs can be used, and how they can be used.

Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience

“…Patients with sustained deep molecular responses achieved more frequently with second-generation TKIs, may be considered for treatment discontinuation [3, 4, 7]. Currently, the National Comprehensive Cancer Network (NCCN) recommend discontinuation for patients in stable molecular response (BCR-ABL1 ≤ 0.01% IS) for ≥ 2 years [8]. Early responses, including BCR-ABL1 ≤ 10% at 3 months, ≤ 1% at 6 months, ≤ 0.1% at 1 year, and ≤ 0.01% later on, have been associated with higher probability of eventually having successful treatment-free remission [9].…”

Análisis de costo-efectividad de nilotinib, dasatinib e imatinib como terapia de primera línea en leucemia mieloide crónica en Colombia, 2012

“…Likewise, publications were identified that served as a basis for knowledge about the natural history of the disease and the technologies assessed. Publications were found that had the objective of assessing recent phase III clinical trials that compared nilotinib or dasatinib with imatinib in recently diagnosed CML (16)(17)(18).…”

“…The branch treated with imatinib was the least expensive option of the three. (12)(13)(14)(15)(16) From total costs, 7.56% was attributed to the treatment of this type of patient, 21.76% to the costs of the technologies analyzed, and adverse events represented 12.13% of the total cost in the different branches, while the remaining 58.55% were progression costs.…”

“…In recent studies these have separately demonstrated superiority to imatinib in terms of progression free survival (PFS) and major molecular response (MMR) as 1st-line treatment in newly diagnosed patients (12)(13)(14)(15)(16) . These efficacy outcomes created the need for a health economics evaluation in Colombia to help in decision making.…”

Fibrosis, Regeneration, and Aging

“…Although more serious complications are relatively rare, prolongation of the QT interval, acute renal failure, and development of Fanconi syndrome have been reported. [41][42][43][44] Some signaling pathways inhibited by these drugs are renoprotective in models of ischemia-reperfusion injury 18,20,24 ; therefore, if clinical trials of cABL inhibitors were to be implemented, renal function would need to be monitored closely. One study suggested a greater decline in renal function in patients who have CML and are treated long term with imatinib than that expected from aging alone.…”