Ibrutinib/Rituximab Combination Leads to High Response Rate Among Patients With CLL
Nearly all of the patients with high-risk chronic lymphocytic leukemia (CLL) in a phase II clinical trial responded to treatment with the targeted therapy ibrutinib (Imbruvica) and the antibody rituximab (Rituxan), researchers reported at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 675).
“This combination improves on the already excellent response rate from ibrutinib alone, which is usually around 70% to 80%. It’s also well tolerated with manageable side effects and significantly improves patients’ quality of life,” said Jan Burger, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston.
Study Details
In the phase II study, 40 patients were treated with ibrutinib at 420 mg daily continuously throughout the study. Rituximab was administered at 375 mg/m2 weekly for the first cycle, then monthly until cycle 6, at which point patients continued on ibrutinib monotherapy.
The ibrutinib/rituximab combination 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%.
Ten percent of responses were complete, but partial responses were substantial, Dr. Burger said. “You can still detect a few CLL cells in the blood or bone marrow, but they don’t cause any symptoms.”
Among a subgroup of 20 patients with either mutated versions of the cancer-suppressing gene TP53 or chromosome 17p deletions, both known indicators of poor prognosis, the combination resulted in a 90% response rate (16 partial and 2 complete responses).
Major Improvement in Quality of Life
Patients reported significant improvement in overall health and quality of life at 6 months, which coincided with weight gain at 3 and 6 months. The proportion of patients reporting high quality of life using EORTC-QOLv.3 questionnaires increased from 46% before treatment to 89% after 6 months of ibrutinib treatment.
The faster, improved response rate, Dr. Burger said, is most likely due to rituximab addressing lymphocytosis, an early effect of ibrutinib treatment that 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 attacks these now more vulnerable CLL cells.
The most common toxicities during treatment were low-grade diarrhea, bruising and rashes, joint pain, nausea, fatigue, and upper respiratory infections. Grade 3 toxicities included lung infections, mucositis, inflammation of the lining of the digestive tract, peripheral neuropathy, and pain and numbness in the hands and feet.
Nine patients withdrew from the study: two due to progressive disease, one from mucositis possibly caused by ibrutinib, two with pneumonia, one due to ear and pulmonary infections, one with Richter’s transformation to an aggressive lymphoma, and one with unrelated progressive respiratory disease and heart failure. One patient died of unknown causes while in remission.
A trial comparing ibrutinib alone to ibrutinib plus rituximab in 208 patients with previously treated CLL is currently underway at MD Anderson.
Dr. Burger receives research funding from Pharmacyclics and serves on an unpaid advisory board for another clinical trial. Senior author Susan O’Brien, MD, also receives research funding from Pharmacyclics.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
