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.
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).