Single-agent ibrutinib shows durable activity in relapsed or refractory mantle-cell lymphoma.

  • Major finding: Single-agent ibrutinib shows durable activity in relapsed or refractory mantle-cell lymphoma.

  • Concept: Inhibition of BTK induced a high response rate and was well tolerated in a phase II trial.

  • Impact: Ibrutinib may improve clinical responses with less toxicity compared with current treatments.

Bruton's tyrosine kinase (BTK) is a critical effector of B-cell receptor signaling that has been implicated in the growth and survival of B-cell malignancies, including mantle-cell lymphoma, an aggressive subtype of non-Hodgkin lymphoma. Preclinical and phase I clinical studies have shown that ibrutinib, an oral, covalent BTK inhibitor, has antitumor activity in animal models and was effective in a small group of patients with mantle-cell lymphoma. To further evaluate the efficacy and safety of ibrutinib as a single-agent therapy, Wang and colleagues performed an open-label phase II trial in 111 patients with relapsed or refractory mantle-cell lymphoma. Patients were classified into two groups based on whether they had received more than two prior treatments with the proteasome inhibitor bortezomib, which is approved for patients who experience disease progression after initial therapy. Single-agent ibrutinib treatment induced an overall response rate of 68%, resulting in a complete response in 21% of patients and a partial response in 47% of patients. Similar response rates were observed in both groups of patients independent of prior bortezomib treatment or risk factors for poor outcome. The median progression-free survival among all patients was estimated to be 13.9 months, and the median overall survival was not reached. Furthermore, the estimated median duration of response was 17.5 months, suggesting that ibrutinib has lasting antitumor activity. Ibrutinib was well tolerated, with the most common treatment-related side effects being grade 1 or 2 adverse events such as diarrhea, fatigue, and nausea; grade 3 or 4 hematologic adverse events were less frequent and included neutropenia and bleeding. These results show that single-agent ibrutinib is highly active in relapsed or refractory mantle-cell lymphoma and suggest that it may be more effective and less toxic compared with currently used treatment regimens for this disease.

Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013 Jun 19 [Epub ahead of print].

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