Redefining Outcomes in NHL Therapy
*RITUXAN Approvals: November 1997, relapsed/refractory, low-grade/follicular NHL; April 2001, weekly dosing x8, bulky disease, retreatment; February 2006, diffuse large B-cell NHL; September 2006, first-line follicular NHL and previously untreated low-grade NHL.
†For relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.
‡For previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy.
§For non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy.
||For previously untreated diffuse large B-cell, CD20-positive NHL (DLBCL) in combination with CHOP or other anthracycline-based chemotherapy regimens.
The first monoclonal antibody therapy approved in the United States for the treatment of cancer, RITUXAN has been used widely and studied extensively since its approval by the Food and Drug Administration in 1997.
1997 — RITUXAN is the first monoclonal antibody therapy approved in the US for cancer†
In 1997, RITUXAN became the first monoclonal antibody approved for the treatment of cancer in the United States, when approval was obtained for the treatment of relapsed or refractory low-grade or follicular, CD20+, B-cell non-Hodgkin's lymphoma. Since the discovery and development of RITUXAN, it has become the focus of extensive clinical research throughout the world.
Since its approval, interest in RITUXAN has continued to grow, with numerous clinical trial research protocols either completed, planned, or in progress investigating RITUXAN in patients with low-grade, intermediate, and high-grade lymphoma. The number of research abstracts and clinical trial reports in the literature has risen sharply over the years, and continues to grow.
Learn more about the weekly x4 trial.
2001 — RITUXAN is approved for retreatment, bulky disease and weekly x8†
In 2001, RITUXAN received approval in the United States with a package insert expanded to include information on the administration of RITUXAN treatment weekly for 8 doses, for the treatment of bulky disease, and for 4 weekly doses as retreatment.
Learn more about RITUXAN's efficacy in relapsed or refractory, low-grade or follicular NHL.
2006 — RITUXAN is approved for previously untreated DLBCL|| with proven overall survival
In February of 2006, RITUXAN was approved for previously untreated DLBCL in combination with CHOP or other anthracycline-based chemotherapy regimens.
Learn more about RITUXAN's efficacy in previously untreated DLBCL with CHOP.
2006 — RITUXAN is approved for previously untreated follicular Non-Hodgkin's Lymphoma (NHL)≠ with proven progression-free survival
In September 2006, RITUXAN received approval for previously untreated follicular, CD20-positive, B-cell NHL in combination with CVP chemotherapy.
Learn more about RITUXAN's efficacy in previously untreated follicular Non-Hodgkin's Lymphoma (NHL) in combination with CVP.
2006 — RITUXAN is approved for low-grade Non-Hodgkin's Lymphoma (NHL)§ with proven risk reduction (risk of progression, relapse or death)
In September 2006, RITUXAN also received approval for the treatment of non-progressing (including stable disease), low-grade, CD20-positive B-cell NHL, as a single agent, after first-line CVP chemotherapy.
Learn more about RITUXAN's efficacy in non-progressing low-grade Non-Hodgkin's Lymphoma (NHL) after CVP.
INDICATIONS AND USAGE
Rituxan® (rituximab) is indicated for the treatment of patients with:
- Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
- 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
BOXED WARNINGS and Additional Important Safety Information
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) patients with Rituxan.
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 fatal hepatitis B reactivation with fulminant hepatitis, other serious viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation.
The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. These infusion reactions generally have resolved with slowing or interruption of the infusion and with supportive care.
Indication-Specific Safety
Single Agent Rituxan for Relapsed or Refractory, Low-Grade or Follicular NHL
The most common adverse reactions of Rituxan (incidence ≥ 25%) observed in patients with relapsed or refractory, low-grade or follicular NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia. Respiratory system events were reported in 38% of patients, and 31% reported infectious events. Grade 3 and 4 cytopenias were reported in 48% of patients and included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%).
Rituxan in Combination with CVP for Previously Untreated, Follicular NHL
Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared to those in the CVP arm. The following adverse reactions occurred more frequently (≥5%) in patients receiving R-CVP compared to 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%).
Single Agent Rituxan for Low-Grade NHL, after First-Line CVP Chemotherapy
The following common adverse reactions were reported more frequently (≥5%) in patients receiving Rituxan following CVP compared with those who received no further therapy: fatigue (39% vs 14%), anemia (35% vs 20%), peripheral sensory neuropathy (30% vs 18%), infections (19% vs 9%), pulmonary toxicity (18% vs 10%), hepatobiliary toxicity (17% vs 7%), rash and/or pruritus (17% vs 5%), arthralgia (12% vs 3%), and weight gain (11% vs 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the Rituxan arm compared with those who received no further therapy (4% vs 1%).
Rituxan in Combination with CHOP Chemotherapy for DLBCL
The following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients age ≥60 years receiving R-CHOP as compared to CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%). In the GELA LNH 98-5 study, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R-CHOP vs. 1.0% for CHOP).
The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R-CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs 7%) and lung disorder (6% vs 3%). Other Grade 3 or 4 adverse reactions reported more frequently among patients receiving R-CHOP were viral infection (GELA LNH 98-5 study), neutropenia (GELA LNH 98-5 and MInT studies), and anemia (MInT study).
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 infusions.
References
- Data on file, F. Hoffmann-La Roche Ltd.
- US National Institutes of Health. Clinicaltrials.gov Web site. Available at: http://www.clinicaltrials.gov/ct/actions/GetStudy. Accessed August 3, 2007.
