One hundred thirty-two patients (74.2%) had been randomized to the experimental treatment arm and had received at least one dose of ibrutinib at the time the data was presented. The median treatment duration was 124 days (4.4 cycles).
Treatment was stopped prematurely in 51 patients. The reasons for early discontinuation were refusal of further treatment (31 patients), toxicity (10 patients), disease progression (5 patients), concomitant use of oral anticoagulants (4 patients), and small cell lung cancer (1 patient).
Among participants in both treatment arms, 29 serious adverse events (SAEs) occurred, including two suspected unexpected serious adverse reactions (SUSARs). Fifteen SAEs (51.7%) were considered related to ibrutinib. SAEs included infections and infestations (10 patients; 34.5%), cardiac disorders (seven patients; 24.1%), musculoskeletal disorders (three patients; 10.3%), vascular disorders (two patients; 6.9%), nervous system disorders (two patients; 6.9%), and five other events.
Severity of the events was classified as mild (5 events; 17.2%), severe (16; 55.2%), life-threatening (5; 17.2%), and one event resulted in death (3.5%). Data on severity was missing for two of these events.
More than half (58.6%) of the SAEs occurred within the first six cycles of treatment. Three patients (10.3%) discontinued treatment, eight patients (27.6%) interrupted treatment, and one patient (3.4%) had the dose reduced due to their SAEs; however, nine patients (31%) did not change their dose.
One SUSAR was a non-ST elevation myocardial infarction. This was reported during the third cycle of treatment in an 82-year-old male patient. This patient had a high comorbidity score that included coronary heart disease, arterial hypertension, diabetes mellitus, and obesity.
The other SUSAR was a cerebral seizure secondary to subdural bleeding. This event occurred in a 78-year-old male patient with a high comorbidity score. He was concomitantly using rivaroxaban, a novel oral anticoagulant. The data safety monitoring board subsequently amended the study to exclude patients using those agents. Patients who were participating in the study could either change anticoagulant or stop the experimental treatment.
The authors concluded that risk in ibrutinib use is acceptable. The study excluded potential subjects with relevant concomitant medication, including vitamin K antagonists, direct Xa-inhibitors, and strong CYP3A4-inhibitors. They stated that, by carefully monitoring subjects for safety, the risks were well-managed in their study.