Even as the targeted therapy ibrutinib makes its way through clinical trials as a single treatment for chronic lymphocytic leukemia (CLL), researchers are studying the new drug in combinations and identifying genomic changes that allow malignant cells to resist treatment.
Jan Burger, M.D., Ph.D., associate professor of Leukemia at The University of Texas MD Anderson Cancer Center, presented two such studies at the 55th Annual Meeting of the American Society of Hematology this month.
Combining ibrutinib with the targeted antibody rituximab resulted in complete or partial responses in 37 of 39 (95 percent) high-risk CLL patients. At a median follow-up of 18 months, 31 patients (78 percent) remained on the drug with no sign of progression, with overall survival at 84 percent.
Genomic analysis of CLL before treatment and after resistance so far point to mutations inside and outside the B cell receptor pathway targeted by ibrutinib as promoting resistance.
"This combination improves on the already excellent response rate from ibrutinib alone, which is usually around 70-80 percent. It's also well-tolerated with manageable side effects and significantly improves patients' quality of life," Burger said.