CLL Dosing Rationale
RITUXAN 375 mg/m2 in Cycle 1 and 500 mg/m2 in Cycles 2-6 of R-FC—proven dosing in CLL
TWO LARGE PHASE III STUDIES RESULTED IN THE INDICATED DOSING IN CLL1
|The only FDA-approved dosing of RITUXAN in the R-FC regimen1*|
|Cycle 1||Cycles 2-6|
|375 mg/m2||500 mg/m2|
given on the day prior to the initiation
of the first cycle of FC chemotherapy
given on Day 1 of subsequent cycles
- *In the R-FC regimen, fludarabine (25 mg/m2 per day) and cyclophosphamide (250 mg/m2 per day) are given on Days 1-3 of all cycles. Each cycle is 28 days in length.1
- CLL=chronic lymphocytic leukemia; R=RITUXAN; FC=fludarabine and cyclophosphamide.
From a biologic standpoint, CLL has important differences from NHL
There is lower expression of CD20 on the surface of B cells in CLL than is seen in follicular lymphoma2,3
There is a higher number of circulating malignant cells in CLL than in follicular lymphoma4-6
The 500 mg/m2 dose of RITUXAN in Cycles 2-6 of the R-FC regimen is supported by data from multiple Phase II and Phase III trials
RITUXAN is not approved as monotherapy in CLL.
- RITUXAN can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion, with time to onset of 30 to 120 minutes
- RITUXAN-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death
- Premedicate patients with an antihistamine and acetaminophen prior to dosing. Depending on the severity of the infusion reaction and the required interventions, slow the infusion rate, interrupt the infusion, or permanently discontinue RITUXAN
- Closely monitor patients with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3)
RITUXAN in combination with FC for previously untreated CLL
- In the CLL8 study of patients with previously untreated CLL, detailed safety data collection was limited to Grade 3 and 4 adverse reactions and serious adverse reactions
- Grade 3 or 4 adverse reactions that occurred more frequently in patients treated with R-FC vs. FC were infusion reactions (9% in the R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%)
- The frequency of prolonged neutropenia for patients who received R-FC vs. FC was 8.5% and 5.8% respectively. For patients who did not have prolonged neutropenia, the frequency of late-onset neutropenia for patients who received R-FC vs. FC was 14.8% and 4.3%, respectively
- Grade 3 or 4 adverse reactions that occurred more frequently in R-FC-treated patients ≥70 years of age compared to younger patients were neutropenia (44% vs. 31%), febrile neutropenia (16% vs. 6%), pancytopenia (7% vs. 2%), and anemia (5% vs. 2%)
RITUXAN in combination with FC for previously treated CLL
- Grade 3 or 4 adverse reactions that occurred more frequently in patients treated with R-FC vs. FC were infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. <1%)
- The frequency of prolonged neutropenia for patients who received R-FC vs. FC was 24.8% and 19.1% respectively. For patients who did not have prolonged neutropenia, the frequency of late-onset neutropenia for patients who received R-FC vs. FC was 38.7% and 13.6%, respectively
- Grade 3 or 4 adverse reactions that occurred more frequently in R-FC-treated patients ≥70 years of age compared to younger patients were neutropenia (56% vs. 39%), infections (30% vs. 14%), anemia (21% vs. 10%), thrombocytopenia (19% vs. 8%), and pancytopenia (7% vs. 2%)
- Fifty-nine percent of R-FC–treated patients experienced an infusion reaction
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2013.
- Almasri NM, Duque RE, Iturraspe J, Everett E, Braylan RC. Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia. Am J Hematol. 1992;40:259-263.
- Yee KWL, O’Brien SM. Chronic lymphocytic leukemia: diagnosis and treatment. Mayo Clin Proc. 2006;81:1105-1129.
- Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute—Working Group 1996 guidelines. Blood. 2008;111:5446-5456.
- O’Brien SM, Kantarjian H, Thomas DA, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol. 2001;19:2165-2170.
- Byrd JC, Murphy T, Howard RS, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol. 2001;19:2153-2164.