LNH 98-5 (GELA) NHL Trial
The first combination to extend DLBCL survival since the 1970s
GELA LNH 98-5 trial: Elderly DLBCL patients1*
Percentages are based on calculations.
*GELA: Groupe d'Etude des Lymphomes de l'Adulte.
†In the GELA trial, the age-adjusted International Prognostic Index (IPI) score, which ranged from 0 to 3, was derived by assigning 1 point for each of the following risk factors: Ann Arbor Stage III or IV, ECOG performance status ≥2, and elevated LDH.
- In the GELA trial, the first Phase III trial to investigate the RITUXAN+CHOP combination, 399 elderly patients were randomized to receive either RITUXAN plus CHOP or CHOP alone as induction therapy1,2
- Baseline patient characteristics were balanced between treatment groups. An IPI score of 2 or 3 (generally associated with a high risk of treatment failure) was observed in 60% of patients in the R-CHOP arm and 61% of patients in the CHOP arm1,3
GELA protocol: R-CHOP x8 vs CHOP x84,5
CHOP dosing frequency and timing (8 cycles q 21 days regardless of early response) were designed to mirror the original clinical trials that established CHOP in DLBCL.4
- Patients were randomized to receive either 8 three-week cycles of CHOP plus RITUXAN 375 mg/m2 given on Day 1 (n=202) or 8 three-week cycles of CHOP alone (n=197)2
Most common adverse reactions in the GELA LNH 98-5 DLBCL clinical trial
- The following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients ≥60 years of age receiving R-CHOP as compared with CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%).5
A significant improvement in survival for elderly patients5,6
GELA overall survival (N=399)5,6
- At 5 years, 8 cycles of RITUXAN+CHOP increased OS from 46% to 58% compared with CHOP alone5
- Eight cycles of RITUXAN+CHOP improved median event-free survival by 164% (2.9 years for R-CHOP vs 1.1 years for CHOP alone with 26-month median follow-up)1,5
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.
- Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242.
- The International Non-Hodgkin's Lymphoma Prognostic Factors Project. A predictive model for aggressive non-Hodgkin's lymphoma. N Engl J Med. 1993;329:987-994.
- Coiffier B, Gisselbrecht C, Reyes F. Rituximab plus CHOP for diffuse large-B-cell lymphoma [letter to the editor]. N Engl J Med. 2002;346:1830-1831.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2010.
- Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005 Jun 20;23(18):4117-26. Epub 2005 May 2.
