A multi-center, international, randomized, Phase III study of older untreated patients with chronic lymphocytic leukemia (CLL) demonstrated that ibrutinib, a kinase inhibitor, is significantly more effective than traditional chemotherapy with chlorambucil.
The study, which followed 269 patients, revealed a 24-month overall survival rate of 97.8 percent for patients taking ibrutinib versus 85.3 percent for those on chlorambucil. Minor adverse effects were reported.
Results from the study, led by Jan Burger, M.D., Ph.D. from The University of Texas MD Anderson Cancer Center, were published in today's online issue of the New England Journal of Medicine.
"Ibrutinib was superior to chlorambucil in CLL patients with no prior treatment, as measured by progression-free survival, overall survival, and response" said Burger, an associate professor in Leukemia. "The study also revealed significant improvements in hemoglobin and platelet levels."
Ibrutinib, marketed as IMBRUVICA® by its developer, Pharmacyclics, an AbbVie Company, was previously FDA-approved for treating mantle cell lymphoma and CLL patients who had relapsed after prior treatments.
"CLL is the most common adult leukemia in western countries, and primarily affects older patients with a median age of 72 years at diagnosis," said Burger. "In many countries, chlorambucil has remained the standard first-line therapy for such patients since the 1960s. This study paves the way for the use of ibrutinib in the front-line therapy setting."
CLL is a disease of B lymphocytes, immune cells that originate in the bone marrow, develop in the lymph nodes, and which fight infection by producing antibodies. In patients with CLL, B cells continuously grow and accumulate in the lymph nodes, bone marrow, and blood, where they crowd out healthy blood cells. CLL cell growth is driven by the B cell receptor (BCR), a molecule on the surface of the leukemia cells, which transmits growth signals into the cells using enzymes, including Bruton's tyrosine kinase (BTK).
Ibrutinib attaches itself to BTK, and thereby blocks BTK function, shutting down the growth signals and consequently leading to CLL cell death. Ibrutinib also disables tissue anchor signals on the leukemia cells, removing CLL cells from the lymph nodes' nurturing environment, causing them to starve.
Patients were randomly assigned to receive either ibrutinib or chlorambucil, both oral medications. Median age of study patients was 72 years, and 44 percent had advanced stage disease. The median follow-up was 18.4 months, with 87 percent of ibrutinib-treated patients still continuing their treatment at the time of analysis. Side effects occurred in 20 percent of patients and included diarrhea, fatigue, cough and nausea.
The study was funded by Pharmacyclics, an AbbVie Company, and was supported in part by the National Institutes of Health (CA016672) and MD Anderson's Moon Shots Program in CLL. This program aims to accelerate the conversion of scientific discoveries into clinical advances and significantly reduce cancer deaths.
Institutions participating in the study included Azienda Ospedaliera Niguarda Cà Granda, University of Rochester, Medical University of Lodz, Copernicus Memorial Hospital, Tom Baker Cancer Centre, Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele, Tel Aviv University, St. James Institute of Oncology, Washington University School of Medicine, Jiangsu Province Hospital, North Shore Hospital, Medical University of Silesia, Kings College Hospital, Royal Bournemouth Hospital, Stanford University School of Medicine, University of Melbourne, Amedeo Avogardo University of Eastern Piedmont, Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine, Norton Cancer Institute, University Hospital Leuven, University Hospital Gent, Fakult?i Nemocnice Brno, University College Hospital Galway, University Clinical Center of Medical University of Gda?sk, University of Oxford, City of Hope National Medical Center, Hebrew University Medical School, Peter MacCallum Cancer Centre and St. Vincent's Hospital, and the University of California San Diego.