B cell receptor inhibitor causes chronic lymphocytic leukemia remission

December 11, 2011

SAN DIEGO - A new, targeted approach to treating chronic lymphocytic leukemia has produced durable remissions in a Phase I/II clinical trial for patients with relapsed or resistant disease, investigators report at the 53rd Annual Meeting of the American Society of Hematology.

"PCI-32765, one of a new class of experimental drugs called B cell receptor inhibitors, has shown impressive potential in this clinical trial for its effectiveness and particularly for its relatively minimal toxicity," said lead investigator Susan O'Brien, M.D., professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center.

According to the National Cancer Institute's Surveillance Epidemiology and End Results database, an estimated 14,570 people will receive a diagnosis of CLL in 2011 and about 4,380 patients will die of the disease.

Six-month progression free survival of 90-92 percent

Of 27 CLL patients treated at a dose of 420 milligrams daily, 70 percent had complete or partial remission at 10.2 months of median follow-up. Six-month progression-free survival was 92 percent. Patients received a median three prior treatments before entering the clinical trial.

At a higher dose of 840 mg, 44 percent of 34 patients achieved complete or partial remission at 6.5 months median follow-up, similar to the response rate of the lower-dose cohort at 6.2 months. Progression free survival at 6 months was 90 percent. Study participants had received a median of five prior treatments.

Overall, five patients (8 percent) of the 61 from both arms had progressive disease and 50 (82 percent) remained on the therapy.

Drug does not suppress blood cell production

CLL presently is treated with combination chemotherapies that can cause myelosuppression - inhibited bone marrow function leading to decreased production of blood cells. The resulting susceptibility to infection can be a problem for patients, O'Brien said.

"PCI-32765 is not myelosuppressive. The main side effect is mild diarrhea that is usually self-limiting," O'Brien said.

Chronic lymphocytic leukemia is caused by overproduction of defective B cell lymphocytes, white blood cells that fight infection by producing antibodies.

PCI-32765 is orally administered and inhibits the Burton's tyrosine kinas (BT) enzyme, which is central to B cell receptor signaling. The drug causes programmed cell death and hinders cell migration and adhesion in malignant B cells.

A Phase III clinical trial is planned. The clinical trial was funded by Pharmacyclics, Inc., the drug's developer.
-end-
Study co-investigators with O'Brien are: Jan Burger, M.D., Ph.D., also of MD Anderson's Department of Leukemia; Kristie Blum, M.D., Amy Johnson, Ph.D., Nyla Heerema, Ph.D., and John Byrd, M.D., of The Ohio State University; Richard Furman, M.D., of Weill Cornell Medical College; Steven Coutre, M.D., of Stanford Cancer Center, Stanford University School of Medicine; Jeff Sharman, M.D., of U.S. Oncology; Ian Flinn, M.D., Ph.D., of Sarah Cannon Research Institute, Nashville, TN; Barbara Grant, M.D., Vermont Cancer Center, University of Vermont, and Tasheda Navarro, Eric Holmgren, Ph.D., and Eric Hedrick, M.D., all of Pharmacyclics, Inc.

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 40 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in "Best Hospitals," a survey published annually in U.S. News & World Report.

University of Texas M. D. Anderson Cancer Center

Related Leukemia Articles from Brightsurf:

New therapeutic approach against leukemia
Using an RNA molecule complex, researchers can prevent retention of cancer stem cell in their tumor supporting niche

Nanoparticle for overcoming leukemia treatment resistance
One of the largest problems with cancer treatment is the development of resistance to anticancer therapies.

Key gene in leukemia discovered
Acute myeloid leukemia (AML) is one of the most common forms of blood cancer among adults and is associated with a low survival rate, and leads to the inhibition of normal blood formation.

Vitamin B6, leukemia's deadly addiction
Researchers from CSHL and Memorial Sloan Kettering Cancer Center have discovered how Acute Myeloid Leukemia is addicted to vitamin B6.

Artificial intelligence tracks down leukemia
Artificial intelligence can detect one of the most common forms of blood cancer - acute myeloid leukemia -- with high reliability.

Milestone reached in new leukemia drug
Using a chemical compound called YKL-05-099, a team of cancer researchers from CSHL and the Dana Farber Institute was able to target the Salt-Inducible Kinase 3 (SIK3) pathway and extend survival in mice with MLL leukemia.

The drug combination effective against bovine leukemia
Scientists have succeeded in reducing levels of the bovine leukemia virus (BLV) in cows with severe infections by combining an immune checkpoint inhibitor and an enzyme inhibitor.

Towards a safer treatment for leukemia
An international team of researchers at VIB-KU Leuven, Belgium, the UK Dementia Institute and the Children's Cancer Institute, Australia, have found a safer treatment for a specific type of leukemia.

Research paves way for new source for leukemia drug
Chemistry researchers have patented a method for making anti-leukemia compounds that until now have only been available via an Asian tree that produces them.

An atlas of an aggressive leukemia
A team of researchers led by Bradley Bernstein at the Ludwig Center at Harvard has used single-cell technologies and machine learning to create a detailed 'atlas of cell states' for acute myeloid leukemia (AML) that could help improve treatment of the aggressive cancer.

Read More: Leukemia News and Leukemia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.