Switching Kinase Inhibitors Shows Favorable Outcomes in Leukemia Therapy

Switching treatments for leukemia from effective kinase inhibitors to an alternative treatment was not found to cause a negative outcome, a recent study indicated.

Researchers from the Perelman School of Medicine at the University of Pennsylvania found that patients with chronic lymphocytic leukemia (CLL) who stopped taking the kinase inhibitors ibrutinib or idelalisib maintained mostly favorable outcomes.

While these drugs have shown impressive results in clinical trials, nearly 30% of patients do not respond to these drugs for reasons unknown.

The researchers sought to determine which alternate therapies are viable for patients if they discontinue ibrutinib or idelalisib, why these patients have to discontinue the drugs, and what are effective alternate treatment options.

"Ibrutinib and idelalisib represent a paradigm shift in management of CLL," said Anthony Mato, MD, MSCE, assistant professor of Hematology/Oncology and director of the Center for Chronic Lymphocytic Leukemia in the Abramson Cancer Center. "But there's a lack of data--real world practice patterns, that is -- for the patients who discontinue these drugs. This is information that may eventually help guide physicians who have patients in similar scenarios. What's the best avenue to treat these patients who fail on one of these therapies? These are the types of questions we wanted to learn more about."

Investigators analyzed 178 patients with CLL from 10 centers throughout the United States. The results showed most patients discontinued ibrutinib or idelalisib as a result of adverse events or due to disease progression.

Most of these patients did not discontinue treatment due to Richter's Transformation, a rare complication in CLL in which the disease evolves into a significantly more aggressive form of large cell lymphoma.

The study further showed that patients who switched to a different kinase inhibitor maintained durable responses, with an objective response rate of 50% and median progression free survival of 11.9 months.

Responses were found to be most durable in patients who stopped treatment due to side effects that caused them to stop taking ibrutinib or idelalisib.