The drug ibrutinib can provide significant anticancer responses with modest side effects in persons with diffuse large B-cell lymphomas (DLBCLs), indicate preliminary results from clinical trials focusing on this aggressive lymphoma subtype.
DLBCLs account for 30% to 40% of newly diagnosed lymphomas. The activated B-cell (ABC) subtype, which makes up approximately 40% of DLBCL cases, has the poorest clinical outcome with current therapy. Although no major treatment advances have been made in more than a decade, researchers have learned that more than 20% of ABC tumors have mutations that alter the activity of the B-cell receptor and promote tumor cell survival in ABC lymphomas.
This molecular research led investigators to enlist ibrutinib (formerly PCI-32765) in clinical trials. Ibrutinib is a potent inhibitor of Bruton’s tyrosine kinase (BTK), a key enzyme in the B-cell receptor pathway that is required for the survival of ABC lymphoma cells. The drug is being developed to target B-cell malignancies, including various forms of leukemia, lymphoma, and multiple myeloma. It was first evaluated in a pilot trial at the National Cancer Institute (NCI) in Bethesda, Maryland, and is now being evaluated in a multicenter study focusing on DLBCL. According to a recent statement from the NCI, results from the pilot trial and individual cases from the ongoing trial indicate that the use of the single-agent pill form of ibrutinib can elicit major antilymphoma effects with minimal side effects.
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In studies led by the NCI’s Louis Staudt, MD, PhD, and Wyndham Wilson, MD, participants were given ibrutinib 560 mg/day until the disease progressed. The drug induced multiple responses including some complete remissions in ABC lymphomas as well as remissions in non-ABC DLBCL. These preliminary results were presented as part of the April 1, 2012, opening plenary session at the American Association of Cancer Research annual meeting, held March 31-April 4, 2012, in Chicago, Illinois. A final analysis will provide more information on the safety and efficacy of ibrutinib.
Investigators are still recruiting participants. Trial details are available at ClinicalTrials.gov (identifier: NCT01325701).
