NHL Weekly x4 Trial (McLaughlin Trial)
Single-agent RITUXAN delivered durable responses in NHL
Original pivotal trial: Heavily pretreated low-grade or follicular NHL1
*Subset analyses conducted on the assessable group of 151 patients; results for the intent-to-treat group were virtually identical.
- In the original multicenter pivotal trial of 166 patients receiving RITUXAN 375 mg/m2 weekly for 4 doses, the complete response (CR) rate was 6%, the partial response (PR) rate was 42%, and the overall response rate (ORR) was 48%2
Safety summary:
- In RITUXAN clinical trials of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL, the most common Grade 3 or 4 adverse reactions (>1%) observed in patients receiving single-agent RITUXAN (N=356) were lymphopenia (40%), neutropenia (6%), leukopenia (4%), infection (4%), anemia (3%), chills (3%), and thrombocytopenia (2%)2
Durable responses achieved despite a median of 3 prior therapies (range 1–10)2
Median duration of response: Pivotal trial (n=80)2
- Prior therapy included chemotherapy in 97%, radiotherapy in 25%, and bone marrow or peripheral-blood stem-cell transplantation in 14% of patients1
Grade 3–4 adverse reactions in patients receiving single-agent RITUXAN
The most common Grade 3 or 4 adverse reactions that occurred more frequently ≥5%) in patients receiving single-agent RITUXAN were lymphopenia (40%), neutropenia (6%), leukopenia (4%), and infection (4%).2
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.
RITUXAN has also been associated with other serious and/or fatal adverse reactions. These include hepatitis B reactivation with fulminant hepatitis, other infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation.
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.
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.
References
- McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-2833.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
