E4494 (NCI) NHL Trial
Survival benefits demonstrated in the NCI-sponsored DLBCL trial
E4494 trial: Elderly DLBCL patients1
Percentages are based on calculations.
*In the E4494 trial, the IPI score, which ranged from 0 to 4, was derived by assigning 1 point for each of the following risk factors: Ann Arbor Stage III or IV, extranodal disease involvement at >1 site, ECOG performance status ≥2, and elevated LDH.
- In the E4494 trial, a North American Phase III trial, 632 elderly patients were given 6 or 8 twenty-one-day cycles of RITUXAN plus CHOP or CHOP alone1,2
E4494 protocol induction: R-CHOP x6–8 vs CHOP x6–81,3
- Patients in the R-CHOP arm received 4 or 5 doses of RITUXAN 375 mg/m2 on Days –7 and –3 (prior to Cycle 1), and 48 to 72 hours pre-Cycle 3, pre-Cycle 5, and pre-Cycle 7 for patients receiving 8 cycles of CHOP induction2
RITUXAN+CHOP prolonged survival in elderly, high-risk DLBCL patients2
- At 2 years, RITUXAN+CHOP increased OS from 63% to 74% compared with CHOP alone2
- RITUXAN+CHOP improved median progression-free survival by 94% (3.1 years for R-CHOP vs 1.6 years for CHOP alone)2
- These results reflect a statistical approach, which allows for an evaluation of RITUXAN administered in the induction setting that excludes any potential impact of RITUXAN given after the second randomization2
Grade 3–4 adverse reactions in the E4494 DLBCL clinical trial
The following Grade 3 or 4 adverse reactions were reported 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%).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.
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.
References
- Data on file, Genentech, Inc.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
- Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:3121-3127.
