Efficacy in Previously Untreated Diffuse
Large B-cell Lymphoma with CHOP*

Prolonging Survival Is One of the Treatment Goals in Appropriate Patients With DLBCL

  • Overall survival (OS) is the definitive clinical trial endpoint in DLBCL [1,2]
  • The best opportunity to achieve durable survival benefits with frontline therapy[3]
  • A complete response does not guarantee prolonged survival
  • RITUXAN® (Rituximab) is the first agent in combination with CHOP to improve survival rates for DLBCL patients since the introduction of CHOP in 1972 [3-5]

RITUXAN Delivers Significant Survival Benefits in DLBCL, as Shown in 3 Large-scale Clinical Trials[4]:

Three randomized, controlled, multicenter studies with a collective enrollment of 1,854 previously untreated DLBCL patients provide powerful support for RITUXAN+CHOP.

Survival Benefits Proven Across a Wide Range of Ages, Disease Stages, and Other Prognostic Factors[4]

a Significant at P<0.05, 2-sided.
b NE=Not reliably estimable.
c Kaplan-Meier estimates.
d R-CHOP vs CHOP.
e CHEMO: Approximately 44% of trial patients in both study arms received CHOEP (CHOP plus etoposide), 49% received CHOP, 4% received MACOP-B (CHOP plus methotrexate and bleomycin), and 4% received PMitCEBO (prednisone, mitoxantrone, cyclophosphamide, etoposide, bleomycin, and vincristine).[6]

LNH 98-5 (GELA) Trial

INDICATIONS AND USAGE

Rituxan® (rituximab) is indicated for the treatment of patients with:

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.

References

1. Armitage JO, Berg AR, Purtilo DT. Adult non-Hodgkin's lymphomas. In: Bick RL, ed. Hematology: Clinical and Laboratory Practice. St. Louis, Mo: Mosby-Year Book, Inc; 1993:875-893.

2. Sunderland MC, Coltman CA. Lymphomas. In: Weiss GR, ed. Clinical Oncology. Norwalk, Conn: Appleton & Lange; 1993:284-298.

3. DeVita VT Jr, Canellos GP, Chabner B, et al. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975;1:248-250.

4. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.

5. Gribben JG, LaCasce AS. Clinical manifestations, staging, and treatment of non-Hodgkin's lymphoma. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; 2005:1397-1419.

6. Data on file, Genentech, Inc.