A step beyond chemo: MD Anderson's key roles in CLL drug approved today

The U.S. Food and Drug Administration today approved ibrutinib as a single treatment for chronic lymphocytic leukemia patients with relapsed or resistant disease.

MD Anderson physicians have been instrumental in the development of the drug, known commercially as Imbruvica, which achieves higher response rates with milder side effects than established treatments for the disease.

They continue to lead clinical trials, including those for new combinations, and lab studies to better understand how ibrutinib works and how drug resistance develops.

"Ibrutinib has distinguished itself by producing durable responses in patients after other treatments have failed and with little toxicity. The main side effect is mild diarrhea which usually resolves over time," says Susan O'Brien, M.D., professor of Leukemia, who led the phase I trial of the drug.

"This is an exciting time for CLL, with ibrutinib and other drugs in clinical trials providing new approaches that move us away from reliance of chemotherapy combinations," O'Brien says.

Milder than chemotherapy

Combinations of chemotherapy and the antibody rituximab have greatly extended survival for many patients in recent years. The standard-of-care combination known as FCR, developed at MD Anderson, puts about one third of patients in remission for 10 years or longer. Even so, chemotherapy side effects remain hard on patients and raise the risk they may develop second cancers down the line.

O'Brien led the phase I clinical trial of ibrutinib and also leads a study of the drug for previously untreated patients over the age of 65, a group that has a particularly hard time with the chemotherapy combinations that have helped many CLL patients.

O'Brien and colleagues reported promising safety and activity of the drug for this group in a recent paper published by the Lancet Oncology.

CLL is a malignancy of immune system B cells, white blood cells that craft antibodies against infection. Ibrutinib blocks Bruton's tyrosine kinase (BTK), a vital component of B cell receptor signaling.

MD Anderson explores new combinations, genomics under Moon Shots Program

An advanced clinical trial of ibrutinib plus rituximab vs.ibrutinib alone opened recently at MD Anderson under the auspices of the CLL Moon Shot, part of the Moon Shots Program to reduce mortality in eight cancers.

The study will enroll 208 previously untreated patients and will include genomic analyses of patients' CLL cells before and during treatment and at the point of disease resistance, if it arises.

Jan Burger, M.D., Ph.D., associate professor of Leukemia, leads the trial, which will reveal how the disease changes during treatment. Burger led a trial of just the ibrutinib and rituximab combination that raised the response rate to 95%, up from 76% with ibrutinib alone.

Burger's lab discovered how ibrutinib pries CLL cells out of their hiding places in lymph nodes and the bone marrow and drives them out into the bloodstream, where they are more easily killed. He is conducting research on CLL resistance to ibrutinib.

CLL is the most common adult leukemia. The American Cancer Society estimates about 15,680 new cases will be diagnosed in 2013 and about 4,580 people will die from the disease.

The U.S. Food and Drug Administration approved the drug for treatment of mantle cell lymphoma last year based on clinical trials led by MD Anderson oncologists. The approval for CLL came via the FDA's accelerated review program for promising therapies.

Imbruvica was developed by Pharmacyclics, Inc., and is marketed by Janssen Biotech Inc., a unit of Johnson & Johnson.