Efficacy in Previously Untreated
Follicular Non-Hodgkin's Lymphoma
in Combination with CVP*

Proven to Prolong Progression-Free Survival With Up to 8 Cycles of R-CVP*

The Marcus (M39021) study was a Phase III multicenter trial designed to evaluate the efficacy of RITUXAN+CVP in previously untreated, advance-stage, follicular NHL.

*CVP is a chemotherapy regimen consisting of cyclophosphamide, vincristine, and prednisolone.


† Percentages are based on calculations

Patients were randomized to receive either 8 three-week cycles of RITUXAN+CVP 375 mg/m2 given on Day 1 (n=162) or 8 three-week cycles of CVP alone (n=160).‡[1,2]


†IWF: International Working Formulation.
‡One patient who was randomized to the CVP arm did not receive study treatment.

Patients showed significant improvement in progression-free survival (PFS) with up to 8 cycles of R-CVP[1,2]


  • R-CVP improved median PFS by 71% (2.4 years for R-CVP vs 1.4 years for CVP alone), with a median follow-up of 18 months [1,2]
  • R-CVP improved 2-year PFS by a relative improvement of 80% (63% for R-CVP vs 35% for CVP alone), with a median follow-up of 18 months [1]
  • R-CVP improved median PFS by 127% (2.83 years for R-CVP vs 1.25 years for CVP alone), with a median follow-up of 53 months [3]

§One patient assigned to the CVP group did not receive any trial medication because the patient withdrew consent.

RITUXAN with CVP yielded significant improvement over CVP alone across a wide range of patient subgroups [1]


CI=Confidence interval. FLIPI=Follicular Lymphoma International Prognostic Index. Bulky disease is defined as any lesion with a diameter >7 cm. Depicted are the univariate hazard rations (HRs) for R-CVP relative to CVP alone, the 95% CI for the HR, and the sample size (n) in each subgroup. The square represents the HR, and the horizontal bar represents the 95% CI. The area of each subgroup is proportional to the number of patients in the subgroup. The dashed vertical line shows the HR for PFS (0.44) in the overall population.[1]

Most frequent adverse reactions observed in the Marcus study

The following adverse reactions, regardless of severity, were reported more frequently (>5%) in patients receiving R-CVP compared to CVP aline: 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%). [2]

Efficacy in Relapsed/Refractory Low-grade or Follicular NHL

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. Data on file, Genentech, Inc.

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

3. Marcus R, Imrie K, Catalano J, et al. Rituximab plus CVP improves survival in previously untreated patients with advanced follicular non-Hodgkin's lymphoma. Paper presented at: American Society of Hematology 48th Annual Meeting and Exposition; December 9-12, 2006; Orlando, Fla. Abstract 481.