Network - Spring 2014
Ibrutinib and rituximab trigger 95% response rate among CLL patients
Nearly all the high-risk chronic lymphocytic leukemia (CLL) patients in a Phase II clinical trial responded to treatment with the targeted therapy ibrutinib and the antibody rituximab,
MD Anderson researchers reported in December at the 55th Annual Meeting of the American Society of Hematology.
CLL is a malignancy of immune system B cells, white blood cells that normally produce antibodies against infection. Ibrutinib blocks Bruton’s tyrosine kinase (BTK), a vital component of B cell receptor signaling.
The combination of ibrutinib and rituximab produced complete or partial responses in 38 of 40 (95%) high-risk CLL patients. At a median follow-up of 18 months, 31 patients (78%) remained on the drug with no sign of progression, with overall survival at 84%.
“This combination improves on the already excellent response rate from ibrutinib alone, which is usually around 70-80%. It’s also well-tolerated, with manageable side effects, and significantly improves patients’ quality of life,” says Jan Burger, M.D., Ph.D., associate professor of Leukemia.
The faster, improved response rate, Burger says, is most likely due to rituximab addressing an early effect of ibrutinib treatment — temporarily higher counts of white blood cells and leukemia cells during the first months of treatment.
Burger’s earlier research showed that this effect occurs because ibrutinib breaks ties that allow leukemia cells to hide out in the bone marrow and in lymph nodes, pushing them out into the bloodstream. Rituximab picks off these now more vulnerable CLL cells.
Similarities in molecular profiles of invasive bladder cancer, breast cancer
Researchers who took a fresh look at muscle-invasive bladder cancer through the lens of gene expression found that it looks remarkably like breast cancer. This has important implications for treating the most lethal form of bladder cancer.
MD Anderson scientists reported in the February edition of Cancer Cell that the gene expression profiles of advanced bladder cancer fall into three molecular categories that closely resemble three of the four major subtypes of breast cancer.
These similarities point to possible chemotherapy guidance and targeted therapy for high-grade disease, says study senior author David McConkey, Ph.D., professor of Urology.
“There are no targeted therapies for this high-grade cancer now, so a future implication of these findings is developing new, better approaches for treating our patients,” McConkey says. Characterization of breast cancer is more advanced, with targeted approaches available for three subtypes and chemotherapy advised for the fourth.
Muscle-invasive disease makes up about 30% of bladder cancer cases, but causes the vast majority of deaths. Treated with chemotherapy, surgery and radiation, the disease will kill about 15,000 Americans this year.
A multi-institutional prospective Phase II clinical trial for muscle-invasive bladder cancer will allow an even more rigorous assessment of the subtypes’ clinical value to guide therapy. Led by the Southwest Oncology Group, the trial will open soon, McConkey says.