On April 21, 2020, the FDA approved the use of ibrutinib (Imbruvica) together with rituximab (Rituxan) for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Ibrutinib is an oral drug that blocks the action of Bruton tyrosine kinase, an enzyme that plays a key role in cancer cells. It has been used by itself and in other combination regimens for patients with CLL or SLL since 2014. Rituximab is an intravenous-administered monoclonal antibody that targets the transmembrane calcium channel CD20 on cancer cells and has been used in chemotherapeutic combinations for CLL since 2010.
The approval of ibrutinib combined with rituximab (IBR + R) was based on data from a large phase 3 clinical trial known as E1912. This randomized study compared the efficacy and safety of IBR + R with the combination of fludarabine, cyclophosphamide, and rituximab (FCR). A total of 529 adults with previously untreated CLL or SLL who required systemic therapy participated in this study. Patients with higher-risk CLL or SLL based on the presence of a specific mutation, 17p deletion, were excluded. Only patients aged ≤70 years were eligible to participate. A total of 354 patients received IBR + R and 175 received FCR. Treatment with IBR + R was given until patients experienced disease progression or until they experienced side effects that were no longer acceptable.1
After treating patients for more than 3 years, the researchers found that IBR + R significantly lengthened patients’ progression-free survival (PFS) compared with FCR. Patients taking IBR + R had a 66% lower risk of CLL progression or death compared with patients taking FCR.
These positive benefits of IBR + R continued after 4 years of follow-up. In addition to improved PFS after 4 years of treatment, patients receiving IBR + R also lived longer than patients receiving FCR, as measured by their overall survival.
The most common side effects reported by patients treated with IBR + R were low levels of platelets (thrombocytopenia), diarrhea, fatigue, muscle and bone pain, low white blood cell counts (neutropenia), rash, low red blood cell counts (anemia), bruising, and nausea. A significantly lower percentage of patients receiving IBR + R (70%) reported at least 1 severe side effect compared with patients receiving FCR (80%).
Based on results of the E1912 clinical trial, the recommended dose of ibrutinib is 420 mg taken orally once daily with a glass of water. Rituximab is given as an intravenous infusion after 1 month of treatment with ibrutinib. Rituximab is administered for a total of 6 cycles (6 months), whereas treatment with ibrutinib continues until disease progression or until side effects become unacceptable.2
With this FDA approval, a new chemotherapy-free treatment regimen is now available for patients with CLL or SLL.
References
- Park B. Imbruvica plus rituximab approved for chronic lymphocytic leukemia. April 23, 2020. www.empr.com/home/news/imbruvica-plus-rituximab-approved-for-chronic-lymphocytic-leukemia/. Accessed June 5, 2020.
- US Food and Drug Administration. FDA approves ibrutinib plus rituximab for chronic lymphocytic leukemia. April 21, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-ibrutinib-plus-rituximab-chronic-lymphocytic-leukemia. Accessed June 5, 2020.
