FROM BLOOD
Ibrutinib is active in patients with previously treated marginal zone lymphoma (MZL) and has a good safety profile, the results of a multicenter, open-label phase II trial published in Blood suggest.
Nearly half of 63 patients responded to monotherapy with the once-daily oral inhibitor of Bruton tyrosine kinase, and ibrutinib was generally well tolerated, according to the study ( Blood. 2017;129:2224-32 ). The results prompted the U.S. Food and Drug Administration to grant accelerated approval of ibrutinib for patients with MZL who were previously treated with at least one prior anti-CD20–based therapy.
“MZL is frequently linked to chronic infection, which may induce B-cell receptor (BCR) signaling, resulting in aberrant B-cell survival and proliferation,” note the investigators, who were led by Ariela Noy, MD , a hematologic oncologist with the Lymphoma Service at the Memorial Sloan-Kettering Cancer Center, New York. “Single-agent ibrutinib induced durable responses with a favorable benefit–risk profile in patients with previously treated MZL, confirming the role of BCR signaling in this malignancy.”
“As the only approved therapy, ibrutinib provides a treatment option without chemotherapy for MZL,” they maintain. “Future studies will investigate ibrutinib in treatment-naive patients or as combination strategies in relapsed/refractory MZL.”
In the trial, which was funded by Pharmacyclics, an AbbVie Company, patients with MZL of all subtypes who had received at least one prior therapy with an anti-CD20 antibody–containing regimen were treated with 560 mg ibrutinib (Imbruvica) orally once daily. The median number of prior systemic therapies was two, and 63% had received prior chemoimmunotherapy.
The overall response rate, as assessed by an independent review committee using 2007 International Working Group criteria – the trial’s primary endpoint – was 48%, according to the published results. Benefit was similar across patients who differed regarding MZL subtype, number of prior regimen, and previous receipt of chemoimmunotherapy
After a 19.4-month median follow-up, the median duration of response was not reached, and median progression-free survival was 14.2 months.
The most common grade 3 or worse adverse events were anemia (14%), pneumonia (8%), and fatigue (6%). Serious adverse events of any grade affected 44% of patients. The most common was grade 3 or 4 pneumonia. Adverse events led to treatment discontinuation in 17% of patients and dose reductions in 10%.
“Due to evidence of pseudoprogression in our trial … biopsies may be warranted to differentiate between true lymphoma progression and immune-mediated antitumor response,” the investigators note.
Dr. Noy disclosed that she has received research funding from Pharmacyclics.
