Adverse Events Caused 81% of Patients to Discontinue TKIs for CML, Study Finds

By Annette M. Boyle, Contributor
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For most patients with chronic myeloid leukemia, the disease means years of ongoing treatment. That makes the impact of adverse effects particularly significant, as researchers in Korea discovered in a study of dasatinib and nilotinib in clinical use.

The researchers found that adverse effects were the most common reason for patients to discontinue use of these tyrosine kinase inhibitors. The study was published in the Blood Journal and presented at the 2016 American Society of Hematology meeting in Atlanta.

The study retrospectively analyzed rates and severity of adverse events in 201 patients with chronic phase CML. All patients received either nilotinib or dasatinib as a first- or second-line therapy at 2 tertiary care centers. The study included 135 men (67%) and 66 women (33%).


120 (60%) patients received nilotinib, 68 as first-line therapy and 52 as second line. 81 (40%) of patients received dasatinib, 37 as first-line and 44 as second-line therapy. About 80% of patients receiving either drug as second-line therapy did so after developing resistance to imatinib.

Over the extended follow up for both groups (8-114 months for nilotinib and 2.2-95 months for dasatinib), 88.3% of patients receiving nilotinib and 86.4% of those receiving dasatinib experienced adverse events. The rate of grade 3-4 AEs was 250% higher in the dasatinib group (54.3%) than in the nilotinib group (21.7%). Grade 3-4 non-hematological AEs occurred at 13%-14% in both groups. Patients receiving dasatinib had more dose reductions, interruptions and discontinuations.

Overall, 58 (29%) of the 201 patients discontinued treatment. AEs accounted for 47 (81%) of the discontinuations with resistance (16%) and other reasons (3%) responsible for the balance. Half of the AEs that led to discontinuation were grade 2. Patients receiving either drug discontinued treatment more quickly in the first-line setting, 2.9 months vs. 15.6 months.

Pleural effusion occurred in 35% of patients receiving dasatinib, leading to discontinuation in half of those cases and accounting for 24% of all discontinuations. An additional patient discontinued dasatinib as a result of pulmonary artery hypertension. Among those receiving nilotinib, stroke, acute coronary syndrome and peripheral artery occlusive disease occurred in 5% of patients and discontinuation occurred only with peripheral artery occlusive disease.

Both drugs had similar progression-free survival on a first- and second-line basis. The dasatinib group had a significantly shorter event-free survival duration, 48.7 months for first-line and 50.5 for second-line, than the nilotinib group, which had not reached event-free survival at the time of the study.

The researchers concluded that CML patients discontinue nilotinib and dasatinib primarily because of adverse events with grade 2 pleural effusion proving particularly hard to manage and contributing to high percentage of discontinuations of dasatinib. Overall, AEs in patients receiving dasatinib led to more discontinuations and significantly shorter event-free survival than in those receiving nilotinib.