Abstract
The Bruton tyrosine kinase inhibitor ibrutinib demonstrated efficacy and safety in early clinical trials for chronic lymphocytic leukemia reported at the annual meeting of the American Society of Hematology.
The Bruton tyrosine kinase inhibitor (BTK) ibrutinib is giving positive preliminary results in treatments for chronic lymphocytic leukemia (CLL), demonstrating efficacy and safety in early clinical trials reported at the annual meeting of the American Society of Hematology (ASH) in Atlanta, GA, on December 8.
The Pharmacyclics once-a-day pill could “significantly change the treatment landscape” for CLL, which is diagnosed in 15,000 people in the United States annually, says John Byrd, MD, professor of medicine and medicinal chemistry at Ohio State University in Columbus and lead investigator of one of the studies.
Although ibrutinib rarely produced complete remission of CLL, it achieved progression-free survival (PFS) for almost 2 years for a substantial majority of the 116 patients in his study. “This drug is working in a new way,” Byrd notes.
BTK is essential to the B-cell receptor (BCR) signaling pathway, and researchers have high hopes that many types of B-cell lymphoma could be successfully treated with drugs that derail that pathway. BTK is commonly seen as the most druggable target in the pathway, and ibrutinib is considered a front-runner in what may emerge as a new class of BTK inhibitors, Byrd says.
At the ASH meeting, Byrd presented findings from a phase Ib/II trial that included 31 CLL patients who were 65 years of age or older whose cancer had not been treated previously with other drugs and 85 patients of various ages for whom standard chemotherapy had failed or produced only a brief remission.
Nearly all (96%) of the previously untreated older patients experienced 22 months of PFS while taking ibrutinib, whereas typically, only half would achieve this survival advantage if they were being treated with standard therapy, according to Byrd. The proportion of patients with cytopenias was also much smaller than typically seen with standard treatment. Results for the previously treated patients (76% PFS at 22 months) were also better than what would be expected with standard therapy, although not quite as impressive as those for the treatment-naïve group.
Another ibrutinib result highlighted at the ASH meeting came from a phase II study designed to assess whether the addition of the anti-CD20 antibody rituximab (Rituxan; Genentech) would boost and accelerate the response to the BTK inhibitor. Results reported by Jan Burger, MD, PhD, associate professor at the University of Texas MD Anderson Cancer Center in Houston, suggest that rituximab will do exactly that.
At the 3-month mark, 17 of 20 CLL patients treated with both therapies had gone into partial remission, according to Burger. The patients enrolled in this study had genetic mutations or chromosomal abnormalities associated with aggressive CLL that resists treatment, so a strong, early response to treatment was considered especially significant.