A two-prong approach combining ibrutinib and rituximab (Rituxin®) to treat aggressive chronic lymphocytic leukemia (CLL) produced profound responses with minor side effects in a Phase 2 clinical trial at the University of Texas MD Anderson Cancer Center.
Researchers presented the results today at the 54th annual meeting of the American Society of Hematology (ASH).
"This is a patient population with a great need for more targeted therapies," said Jan Burger, M.D., Ph.D., associate professor in MD Anderson's Department of Leukemia. Burger was lead author of the study.
"Many CLL patients, especially those with indolent or non-aggressive disease, do well on the standard treatment of chemotherapy and antibodies," he said. "But for a certain subset of high-risk patients, treatment often fails, and remissions, if they are achieved, are short."
According to the National Cancer Institute's Surveillance Epidemiology and End Results database, CLL is the most common type of adult leukemia in the United States. An estimated 16,000 new cases will be diagnosed this year, and about 4,600 people will die because of the disease. Median age of diagnosis is 72, and it is more common in men than women.
Although chemotherapy combinations have improved the cure rate for CLL, side effects often are severe. A sizeable number of CLL deaths are from secondary cancers caused by treatment.
Early studies showed potential
Ibrutinib, a tyrosine kinase inhibitor that thwarts B-cell receptor signaling, is a promising new targeted therapy for mature B-cell malignancies, including certain types of myeloma and lymphoma. It has been shown to be especially effective in CLL.
Over the past two years, Phase 1/2 trials at MD Anderson and other sites showed high-risk CLL patients responded as well as low-risk patients to ibrutinib. However, the response often is lessened because of persistent lymphocytosis, an increase in leukemia cells in the blood due to release of CLL cells from the tissues (lymph glands) into the blood stream. Rituximab, a well-established antibody, was added to capture the CLL cells in the blood and thereby accelerate and improve response.
"When we looked at how well the high-risk patients were doing on ibrutinib - even though it was a small number - we saw a great opportunity to find out if combining the two drugs would have a positive impact on these patients," Burger said.
Combination tolerated wellForty patients with high-risk CLL were enrolled in the study earlier this year. They received:
Preliminary results: 85 percent response rate
Of 20 patients evaluated for early response at three months, 17 achieved partial remission for an overall response rate of 85%. Three achieved partial remission with persistent lymphocytosis.
Interestingly, lymphocytosis peaked earlier and the duration was shorter than with ibrutinib alone.
Treatment was well tolerated, with 13 cases of grade 3 or grade 4 toxicities, including neutropenia, fatigue, pneumonia, insomnia and bone aches. Most side effects were unrelated and transient. Many patients reported improved overall health and quality of life after three cycles of treatment.
"Although this study has a short follow-up time, we are encouraged by the fact that the vast majority of patients are responding and are able to continue on treatment, Burger said.
Development of ibrutinib for CLL crucial
Researchers said these data, together with the previous Phase 1/2 studies, emphasize the need for rapid further development of ibrutinib for high-risk CLL patients.
Pharmacyclics, the company that is developing ibrutinib, is proceeding with a Phase 3 multi-center clinical trial, in which MD Anderson will participate. Additionally, MD Anderson researchers will conduct a follow-up study on their research in high-risk CLL patients.
Other research team members from MD Anderson's Department of Leukemia included Michael Keating, M.D.; William Wierda, M.D., Ph.D.; Julia Hoellenriegel, M.S.; Alessandra Ferrajoli, M.D.; Stefan Faderl, M.D.; Susan Lerner, M.S.; Gracy Zacharian; Hagop Kantarjian, M.D.; and Susan O'Brien, M.D. Also participating were Xuelin Huang, Ph.D., of the Department of Biostatistics at MD Anderson; and Danelle James, M.D. and Joseph Buggy, Ph.D., of Pharmacyclics, Inc, Sunnyvale, CA.
Support for the study was provided by Pharmacyclics and CLL Global Research Foundation.
About MD Anderson
The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For nine of the past 11 years, including 2012, MD Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.
Scott Merville | EurekAlert!
'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS
New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy