Abstract
The outcomes for patients with chronic myeloid leukemia have improved dramatically with the development and availability of BCR–ABL1 tyrosine kinase inhibitors (TKIs) over the past decade. TKI therapy has a superior safety profile compared with the previous standard of care, interferon-α, and most adverse events (AEs) observed with front-line and second-line TKI treatment are managed with supportive care. However, some patients are intolerant to TKI therapy and experience AEs that cannot be managed through dose reduction or symptomatic treatment. Careful management of AEs helps patients to remain adherent with treatment and increases their chances for successful outcomes. Proactive vigilance for potential AEs and treatment strategies that reduce symptom burden will help to minimize patient intolerance. This review discusses the most common AEs associated with intolerance to TKI therapy and treatment strategies to help manage patients at risk for or experiencing these events.
Highlights
The tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA) has transformed the treatment of patients with chronic myeloid leukemia (CML)
The analysis demonstrated that 4% of imatinibintolerant patients developed similar nonhematologic toxicity with dasatinib, only 1% discontinued treatment; dose reduction was sufficient for management of most adverse event (AE).[45]
The discontinuation rate because of toxicity was slightly higher than that observed in the DASISION study for both dasatinib- and imatinib-treated patients, 15% and 11%, respectively, but the overall AE profile was similar to that reported in the DASISION
Summary
The tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA) has transformed the treatment of patients with chronic myeloid leukemia (CML). With respect to cardiac AEs, prolongation of QT interval corrected by Fridericia’s formula (QTcF)24 4500 ms was observed in four (1.2%) patients with CML-CP25 in a phase study and in no patients with CML-AP.[21,22] Data at 24 months indicated that the safety profile in the longer term was unchanged, and nilotinib retained its favorable risk/benefit ratio.[25] Cases of peripheral arterial occlusive disease occurring during nilotinib treatment have been identified, mostly in the second-line setting.
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