Patients with marginal zone lymphoma (MZL) who underwent prior therapy with an anti-CD20 antibody regimen may be treatable with a tyrosine kinase inhibitor approved for other blood cancers, according to research published in Blood (published online January 2017; doi:10.1182/blood-2016-10-747345).
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MZL is a heterogeneous B-cell malignancy for which no standard treatment exists. Bruton’s tyrosine kinase (BTK) is central to the B-cell receptor (BCR) pathway and is a critical component not only of B-cell malignancy growth but also the survival and migration of malignant B-cells. BTK is a potential biomarker target in MZL, but specific data and research is limited.
Ariela Noy, MD, PhD, Memorial Sloan Kettering Cancer Center (New York, NY), and colleagues investigated the efficacy and safety of ibrutinib – a BTK-inhibitor approved for the treatment of chronic lymphocytic leukemia and other blood malignancies – in patients with MZL previously treated with chemo-immunotherapy. Researchers sampled 63 patients with MZL of all subtypes who received one or more prior therapies to receive ibrutinib (560 mg/day, orally) until progression or unacceptable toxicity. The primary endpoint was overall response rate.
Results of the study showed a 48% overall response rate (95% CI, 35-62) in 60 of the evaluable patients. With a median follow-up of 19.4 months, median duration of response was not reached (95% CI, 16.7-NE) and median progression-free survival was 14.2 months (95% CI, 8.3-NE).
Adverse events were reported as a result of ibrutinib treatment, including grade 3 events such as anemia (14%), pneumonia (8%), and fatigue (6%) among 42 patients (67%). Serious adverse events of any grade occurred in 44% of patients, with grade 3-4 pneumonia being the most common. Adverse events led to 17% discontinuation of treatment and 10% dose reductions among all patients.
Researchers concluded that single-agent ibrutinib confirmed the role of BCR signaling in patients with previously treated MZL. “Given the current lack of approved therapies for patients with MZL, ibrutinib may represent a new treatment option with a favorable benefit-risk profile and convenient, once-daily oral administration,” they wrote.
Ibrutinib was approved by the FDA on January 19, 2017. Further research will investigate ibrutinib in treatment-naïve patients or in combination therapies in relapsed and refractory MZL. – Zachary Bessette
