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Jennifer R. Brown, MD, PhD


CLL12 Trial: Use of Ibrutinib in Early-Stage CLL

By: Joseph Fanelli
Posted: Friday, February 18, 2022

Based on the findings of the phase III CLL12 trial, presented in the journal Blood, although ibrutinib is effective as a treatment for patients with early-stage chronic lymphocytic leukemia (CLL), the latest results do not justify amending the current standard of “watch and wait” or observing for signs of progressive bone marrow failure or symptoms caused by the disease. The modification of this strategy would require a significant survival benefit from treatment with ibrutinib, which was not seen, observed Michael Hallek, MD, of the University of Cologne, Germany, and colleagues.

“The CLL12 results confirm the cardiovascular toxicity of ibrutinib,” the authors concluded. “The high incidence of adverse events observed in the placebo group demonstrated that even early-stage, untreated CLL may be associated with relevant morbidity.”

In this place-controlled trial, the authors assigned patients with asymptomatic, treatment-naive Binet stage A CLL to be treated with 420 mg of ibrutinib per day (182 patients) or a placebo (181). All patients were evaluated as being at an increased risk of disease progression.

After a median follow-up of 31 months, the authors found that event-free survival in patients treated with ibrutinib was significantly improved compared with the placebo (not reached vs. 47.8 months, respectively). Compared with the placebo, ibrutinib did not increase overall toxicity among patients, yielding a similar incidence and severity of adverse events, the most common of which were atrial fibrillation, pneumonia, and rash. The most common serious adverse events in the placebo cohort were basal cell carcinoma, pneumonia, and myocardial infarction.

For those who received ibrutinib, the risk for bleeding was decreased (33.5%) by prohibiting the use of oral anticoagulants through an amendment of the study protocol and by avoiding CYP3A4 drug-to-drug interactions.

Disclosure: For a full disclosure of the study authors, visit

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