Previously Untreated Follicular NHL
Prolonged PFS in untreated follicular Non-Hodgkin's Lymphoma (NHL)
Marcus (M39021) study: Previously untreated, advanced-stage patients1
Percentages are based on calculations.
*CVP=cyclophosphamide, vincristine, and prednisolone.
- The Marcus study was a Phase III, multicenter trial designed to evaluate the efficacy of RITUXAN+CVP in previously untreated, advanced-stage, follicular NHL2
Marcus protocol: R-CVP x8 vs CVP x83
†IWF: International Working Formulation.
‡One patient who was randomized to the CVP arm did not receive study treatment.
- Proven regimen for first-line therapy: Patients were randomized to receive either 8 three-week cycles of RITUXAN 375 mg/m2+CVP given on Day 1 (n=162) or 8 three-week cycles of CVP alone (n=160)1,2‡
- 85% of patients received 8 cycles of R-CVP; 68% received 8 cycles of CVP alone1
Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared with those in the CVP arm.2
Up to 8 cycles of RITUXAN plus CVP significantly improved PFS over CVP alone
Marcus (M39021) study (N=322)3
§One patient assigned to the CVP group did not receive any trial medication because this patient withdrew consent.
- 127% improvement in median PFS: 2.83 years R-CVP vs 1.25 years CVP (53-month median follow-up)4
- 113% improvement in median PFS: 2.67 years R-CVP vs 1.25 years CVP (30-month median follow-up)3
- 80% relative improvement in 2-year PFS: 63% R-CVP vs 35% CVP (18-month median follow-up)1
Safety summary:
- Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared with those in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared with CVP alone: rash (17% vs 5%), cough (15% vs 6%), flushing (14% vs 3%), rigors (10% vs 2%), pruritus (10% vs 1%), neutropenia (8% vs 3%), and chest tightness (7% vs 1%)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
- Data on file, Genentech, Inc.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
- Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105:1417-1423.
- Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisolone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26:4579-4586.
