Researchers Detail Reasons for Ibrutinib Therapy Discontinuation in Some Patients with CLL

Research at Ohio State and elsewhere has shown the drug ibrutinib to be highly effective among certain patients with chronic lymphocytic leukemia (CLL), but a study at the OSUCCC – James has shown that about 10 percent of patients discontinued the drug because of disease progression.

CLL is the most common form of chronic leukemia among adults, with 14,600 new cases expected this year. The malignancy remains incurable, but advances in therapy have been made. One of which is the emergence of kinase inhibitors such as ibrutinib for patients who have relapsed or for those whose disease is resistant to other therapies.

Ibrutinib, marketed as Imbruvica®, is the first drug to target Bruton tyrosine kinase, a protein essential for CLL cell survival and proliferation. Work by OSUCCC – James researchers played a key role in gaining FDA approval of ibrutinib to treat certain patients with CLL or mantle cell lymphoma.

Clinical studies of this drug have continued, including a Pelotonia-supported study published in the Journal of the American Medical Association (JAMA) Oncology. The study by OSU hematologists Kami Maddocks, MD, Jennifer Woyach, MD, and colleagues studied the outcomes of patients who discontinued ibrutinib therapy during four sequential clinical trials involving 308 patients at the OSUCCC – James. They found that of the 308 patients in the study, 31 stopped ibrutinib due to disease progression.

The first of its kind, this study provides insight into baseline factors associated with ibrutinib discontinuation. "This data enhance our understanding of how patients do on ibrutinib on a long-term basis and who is likely to relapse," says Woyach, the study’s senior author and a member of the OSUCCC – James Leukemia Research Program.

"Many patients have durable remissions with ibrutinib, and understanding which patients are at higher risk helps us select who might benefit from clinical trials on other new agents and combination therapies rather than starting ibrutinib treatment by itself," she adds. "We have confirmed that specific gene mutations are seen in patients who relapse, which gives us an idea of other drugs that might be effective in these circumstances."