An interim analysis of a large phase 3 clinical trial has found that the combination of ibrutinib plus rituximab was superior to standard treatment for people age 70 and younger with previously untreated chronic lymphocytic leukemia, or CLL. The trial met its primary endpoint of an improvement in progression-free survival (the length of time people live before their disease worsens). The combination also improved overall survival, the trial’s secondary endpoint.
In general, people prescribed the ibrutinib–rituximab combination were less likely to experience serious side effects than were those who received the standard treatment. Until now, the standard treatment for previously untreated CLL has been a six-month course of FCR, which combines the chemotherapy drugs fludarabine and cyclophosphamide with rituximab.
The findings were presented as a late-breaking abstract at the American Society of Hematology annual meeting in December. The trial was sponsored by the National Cancer Institute, part of the National Institutes of Health, and designed by researchers with the ECOG-ACRIN Cancer Research Group.
“These results are practice-changing and immediately establish ibrutinib and rituximab as the new standard of care for the initial treatment of CLL in patients age 70 and younger,” says lead investigator Tait Shanafelt, MD, a professor of hematology at the Stanford University School of Medicine in Palo Alto, CA. “The E1912 trial showed that the combination of ibrutinib and rituximab not only provided better leukemia control, it also prolonged life and had fewer side effects.”
“These definitive results show why large trials like this, that test new therapies in an effort to achieve clinically meaningful benefit for patients, are so important,” says Richard F. Little, MD, of the Cancer Therapy Evaluation Program at the National Cancer Institute.
Ibrutinib and rituximab are targeted treatments. Ibrutinib interferes with the survival of lymphocytic leukemia cells, and rituximab enhances the ability of the body’s immune system to destroy the cells. Ibrutinib is approved by the U.S. Food and Drug Administration for the treatment of some blood cancers, including CLL.
Findings from another NCI-supported trial on ibrutinib in people with CLL were also presented at the ASH meeting and published in The New England Journal of Medicine. The A041202 trial – an international phase 3 clinical trial coordinated by the Alliance for Clinical Trials in Oncology – demonstrated that ibrutinib produces superior progression-free survival compared with standard chemoimmunotherapy (bendamustine plus rituximab) in people with previously untreated CLL who are age 65 and older. The study found that adding rituximab to ibrutinib did not improve progression-free survival beyond ibrutinib alone.
“These two NCI-funded trials have collectively established ibrutinib-based therapy as the first line treatment for CLL patients of any age,” notes Dr. Little.