03:42am Saturday 29 February 2020

Chronic Lymphocytic Leukemia Patients Who Switched Kinase Inhibitors Had Favorable Outcomes

ORLANDO— Chronic lymphocytic leukemia (CLL) patients who stopped taking the kinase inhibitors (KIs), ibrutinib or idelalisib, had mostly favorable outcomes when they switched to the alternate therapy, according to large multi-center study, conducted in part at the Perelman School of Medicine at the University of Pennsylvania.

The results will be presented by Anthony Mato, MD, MSCE, an assistant professor of Hematology/Oncology and the and director of the Center for Chronic Lymphocytic Leukemia in the Abramson Cancer Center, at the 57th annual meeting of the American Society of Hematology (Abstract 719).

While clinical studies have well documented the impressive efficacy of ibrutinib and idelalisib, two drugs approved by the U.S. Food and Drug Administration over the past year, little is known about the nearly 30 percent of patients who do not respond to those treatments, particularly outside the context of clinical research.

What alternate therapies are patients prescribed when they discontinue ibrutinib or idelalisib? Why do patients have to discontinue the drugs? Is the alternate KI effective? What are their outcomes? These are some of the key questions the team aimed to answer.

 “Ibrutinib and idelalisib represent a paradigm shift in management of CLL,” Mato said. “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.”

The researchers performed a retrospective analysis of 178 CLL patients from 10 centers across the United States. It revealed that a majority of the patients discontinued ibrutinib or idelalisib because of side effects or because their cancer progressed while taking the drugs, not Richter’s Transformation, a rare complication of CLL characterized by the sudden transformation of the disease into a significantly more aggressive form of large cell lymphoma.

Patients who discontinued ibrutinib or idelalisib and went on to be treated with the other KI had durable responses, the researchers report. The objective response rate was 50 percent and median progression free survival was 11.9 months.  Responses were most durable for patients who discontinued ibrutinib or idelalisib because they experienced side effects that made it difficult for them to continue taking the drug.

A clinical trial targeting this so-called “KI intolerant” patient population will be undertaken to validate these findings prospectively, the authors said.

Penn co-authors include Stephen Schuster MD, the Robert and Margarita Louis-Dreyfus Associate Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research, David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Jakub Svoboda, MD, an assistant professor of Hematology/Oncology, Sunita Dwivedy Nasta, MD, an associate professor of Hematology/Oncology, and Daniel J. Landsburg, MD, an assistant professor of Hematology/Oncology.

Editor’s note: Dr. Mato has research support from Pharmacyclics LLC and Gilead.


Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2014, Penn Medicine provided $771 million to benefit our community.

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