GELA LNH 98-5 Trial

Up to 8 cycles of RITUXAN+CHOP significantly improved OS for elderly DLBCL patients

GELA TRIAL DESIGN: R-CHOP ×8 VS CHOP ×81,2

Chart: GELA Trial Design: R-CHOP x8 vs CHOP x8
  • CHOP=cyclophosphamide 750 mg/m2 on Day 1, doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 on Day 1; prednisone 40 mg/m2/day on Days 1 through 5. R=RITUXAN 375 mg/m2, given on the first day of each CHOP cycle. Randomization was stratified by the IPI score. Tumor response was assessed after the eighth cycle of treatment or at the end of treatment.2
  • GELA=Groupe d’Etude des Lymphomes de l’Adulte; OS=overall survival; DLBCL=diffuse large B-cell lymphoma.

GELA TRIAL: ELDERLY DLBCL PATIENTS2

Baseline patient characteristics R-CHOP
(n=202) 		CHOP
(n=197)
Age range (years) 59-80 60-80
Median age 70 69
Elevated LDH (>1×ULN) 65% 67%
Ann Arbor Stage I/II III/IV 20%
79% 		21%
80%
ECOG performance status 0-1 2-3 78%
22% 		84%
17%
Bulky disease (>10 cm) 30% 33%
Extranodal involvement (≥2) 52% 52%
IPI score* <2 ≥2 40%
60% 		39%
61%
  • *In the GELA trial, the age-adjusted 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.
  • LDH=lactate dehydrogenase; ULN=upper limit of normal; ECOG=Eastern Cooperative Oncology Group; IPI=International Prognostic Index.

GELA TRIAL: OVERALL SURVIVAL AT 5-YEAR MEDIAN FOLLOW-UP (N=399)2,3

Chart: GELA Trial: Overall Survival at 5-Year Median Followup (N=399)
  • OS, with a median follow-up of 5 years, was 58% for 8 cycles of R-CHOP vs 46% for CHOP alone1
  • 164% improvement in the primary endpoint of event-free survival at 2-year follow-up (2.9 years vs 1.1 years, p<0.001)1

Safety for RITUXAN in combination with CHOP chemotherapy for DLBCL

  • Detailed safety data collection in these trials was primarily limited to Grade 3 and 4 adverse reactions and serious reactions. In studies of elderly patients with DLBCL, 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%)
  • In one of the studies of elderly patients, GELA LNH 98-5, 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)

References:
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012.
  2. 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.
  3. 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;23:4117-4126.

Indications

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 first-line chemotherapy and, in patients achieving a complete or partial response to RITUXAN in combination with chemotherapy, as single-agent maintenance therapy
  • 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
  • Previously untreated and previously treated CD20-positive CLL in combination with fludarabine and cyclophosphamide (FC)

RITUXAN is not recommended for use in patients with severe, active infections.

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) 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 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 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 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 CLL 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.