Patients with advanced-stage marginal-zone lymphoma (MZL) often relapse and the disease is generally incurable. Until now, no standard-of-care or FDA-approved therapeutic options are available. B-cell receptor (BCR) signalling comprises a critical component of tumour growth and survival; Bruton tyrosine kinase (BTK) is central to this pathway. Ibrutinib, an oral inhibitor of BTK, has activity and is FDA-approved in a variety of B-cell malignancies and might be an effective treatment for MZL.

Ariela Noy explains the promise of ibrutinib in MZL: “having an oral non-cytotoxic option is valuable in patients with a chronic lymphoproliferative disorder, who can expect to live a long time with their disease.” Thus, Noy and co-authors initiated an open-label, multicentre, phase II trial of this agent and enrolled 60 patients with MZL who had received at least one prior therapy. The overall response rate was 48% with a median duration of response not reached after a median follow-up duration of 19.4 months. “This is the first prospective study to include patients with all subtypes of MZL. The results achieved are comparable to those of ibrunitib in other relapsed or refractory non-Hodgkin lymphoma settings,” Noy states. The overall response and clinical benefit rates, as well as the duration of response, were meaningful with an expected adverse-event profile.

While a direct comparison to other approaches is not possible in a nonrandomized trial, ibrutinib represents a treatment option for relapsed/refractory MZL. The trial led to FDA approval for this indication. As this treatment is associated with a favourable benefit–risk profile and provides the convenience of once-daily oral administration, another study is underway to assess ibrutinib in the first-line treatment of MZL.