Now Approved for CLL
RITUXAN® (Rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL).
RITUXAN is not recommended for use in patients with severe, active infections.
R=RITUXAN; PFS=progression-free survival.
- *
- In the REACH trial, patients had received 1 prior therapy. Patients who had previously received RITUXAN or both fludarabine and cyclophosphamide, either sequentially or in combination, were excluded from the trial, as were fludarabine-refractory patients; alkylator-refractory patients were permitted.2
In the CLL8 trial1
- RITUXAN+FC provided a median PFS of 3.3 years in first-line CLL (p<0.01)
In the REACH trial1
- RITUXAN+FC provided a median PFS of 2.2 years in previously treated CLL (p=0.02)
Treatment Considerations
These trials were not designed or powered to detect a significant difference in PFS by age category. However, exploratory analyses defined by age suggest no observed benefit with the addition of RITUXAN to FC chemotherapy in previously untreated CLL patients 70 years of age or older and in previously treated CLL patients 65 years of age or older.1
RITUXAN safety profile in combination with FC1,2
First-line CLL
Grade 3 and 4 adverse reactions
- In the CLL8 trial of first-line CLL, Grade 3 and 4 adverse reactions occurred in 77% of R-FC–treated patients vs 62% of FC-treated patients2
- The most frequent (≥25%) Grade 3 or 4 adverse reaction in both arms was neutropenia2
- Safety data collection in CLL8 was limited to Grade 3 and 4, and serious adverse reactions1
Grade 3 and 4 adverse reactions, R-FC vs FC
- Grade 3 or 4 adverse reactions that occurred more frequently (≥2%) in patients treated with R-FC vs FC were neutropenia (30% vs 19%), febrile neutropenia (9% vs 6%), leukopenia (23% vs 12%), and pancytopenia (3% vs 1%)1
- Grade 3 or 4 infusion-related adverse reactions† occurred in 9% of patients treated with R-FC1
- Grade 3 or 4 infections observed during the trial were similar between treatment arms (18% R-FC vs 17% FC)2
Adverse reactions in patients ≥70 years of age
- Grade 3 or 4 adverse reactions that occurred more frequently in R-FC–treated patients ≥70 years of age compared with R-FC–treated patients <70 years of age were neutropenia (44% vs 31%), febrile neutropenia (16% vs 6%), pancytopenia (7% vs 2%), and anemia (5% vs 2%)1
Previously treated CLL
Most common adverse reactions
- The most common (≥25%) adverse reactions in the R-FC arm were neutropenia, nausea, and pyrexia2
Grade 3 and 4 adverse reactions
- Grade 3 or 4 adverse reactions occurred in 80% of R-FC–treated patients vs 74% of FC-treated patients2
- The most frequent (≥25%) Grade 3 or 4 adverse reaction in both arms was neutropenia2
Grade 3 and 4 adverse reactions, R-FC vs FC
- Grade 3 or 4 adverse reactions that occurred more frequently (≥2%) in patients treated with R-FC vs FC were neutropenia (49% vs 44%), febrile neutropenia (15% vs 12%), thrombocytopenia (11% vs 9%), hypotension (2% vs 0%), and hepatitis B (2% vs <1%)1
- Grade 3 or 4 infusion-related adverse reactions† occurred in 7% of patients treated with R-FC1
- Grade 3 or 4 infections observed during the trial were similar between treatment arms (18% R-FC vs 19% FC)2
Adverse reactions in patients ≥70 years of age
- Grade 3 or 4 adverse reactions that occurred more frequently in R-FC–treated patients ≥70 years of age compared with R-FC–treated patients <70 years of age were neutropenia (56% vs 39%), infections (30% vs 14%), anemia (21% vs 10%), thrombocytopenia (19% vs 8%), and pancytopenia (7% vs 2%)1
- †
- Infusion-related adverse reactions were defined as any of the following adverse reactions occurring within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea.1
References
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
- Data on file, Genentech, Inc.
INDICATIONS AND IMPORTANT SAFETY INFORMATION
RITUXAN® (Rituximab) is indicated for the treatment of patients with:
- Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
- Weekly ×4
- Weekly ×8
- Bulky disease
- Retreatment
- Previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy
- Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy
- Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens
RITUXAN is not recommended for use in patients with severe, active infections.
WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
Infusion Reactions: RITUXAN administration can result in serious, including fatal, infusion reactions. Deaths within 24 hours of RITUXAN infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue RITUXAN infusion and provide medical treatment for Grade 3 or 4 infusion reactions.
Tumor Lysis Syndrome (TLS): Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non-Hodgkin’s lymphoma (NHL) with RITUXAN monotherapy.
Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN.
Progressive Multifocal Leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving RITUXAN.
WARNINGS AND PRECAUTIONS
RITUXAN has also been associated with other serious and/or fatal adverse reactions. These include
- hepatitis B reactivation with fulminant hepatitis; hepatic failure resulting in death
- serious, including fatal, bacterial, fungal, and new or reactivated viral infections
- cardiovascular events, including serious or life-threatening cardiac arrhythmias
- severe, including fatal, renal toxicity
- abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy
Additional Important Safety Information
- The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions typically resolved with slowing or interruption of the infusion and with supportive care. The most frequent Grade 3 or 4 adverse reactions observed in NHL were cytopenias, including lymphopenia
- The most common adverse reactions of RITUXAN (incidence ≥25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia. Infusion-related adverse reactions occurring during or within 24 hours of the start of infusion included nausea, pyrexia, chills, hypotension, vomiting, and dyspnea. Most patients treated with R-FC experienced at least one Grade 3 or 4 adverse reaction. The Grade 3 or 4 adverse reactions observed more frequently with R-FC compared with FC alone were neutropenia, leukopenia, febrile neutropenia, thrombocytopenia, infusion reactions, pancytopenia, hypotension, and hepatitis B
- In clinical trials, CLL patients 70 years of age or older who received R-FC had more Grade 3 and 4 adverse reactions compared with younger CLL patients who received the same treatment
For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.
Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.
