Prolonged PFS in untreated follicular Non-Hodgkin's Lymphoma
Marcus (M39021) study: Previously untreated, advanced-stage patients1
Percentages are based on calculations.
*CVP: Cyclophosphamide, vincristine, and prednisolone.
- The Marcus study was a Phase III, multicenter trial designed to evaluate the efficacy of RITUXAN+CVP in previously untreated, advanced-stage, follicular NHL2
Marcus study protocol1: R-CVP x8 vs CVP x8
†IWF: International Working Formulation.
‡One patient who was randomized to the CVP arm did not receive study treatment.
- Proven regimen for first-line therapy: Patients were randomized to receive either 8 three-week cycles of RITUXAN 375 mg/m2+CVP given on Day 1 (n=162) or 8 three-week cycles of CVP alone (n=160)‡1,2
- 85% of patients received 8 cycles of R-CVP; 68% received 8 cycles of CVP alone1
Patients in the R-CVP arm had higher incidences of infusional toxicity and of neutropenia as compared to those in the CVP arm.2
Up to 8 cycles of RITUXAN plus CVP significantly improved PFS over CVP alone
Marcus (M39021) study (N=322)1,3
§One patient assigned to the CVP group did not receive any trial medication because this patient withdrew consent.
- 127% improvement in median PFS: 2.83 years R-CVP vs 1.25 years CVP (Marcus M39021 study: 53-month median follow-up)3
- 71% improvement in median PFS: 2.4 years R-CVP vs 1.4 years CVP (18-month median follow-up)1,2
- 80% relative improvement in 2-year PFS: 63% R-CVP vs 35% CVP (18-month median follow-up)1
PFS benefit across a wide range of patient subgroups1
Marcus subset analysis: Significant PFS benefit with R-CVP1
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 ratios (HRs) for R-CVP relative to CVP alone, the 95% CI for the HR, and the sample size (n) in each subgroup. The circle represents the HR, and the horizontal bar represents the 95% CI. The area of each circle 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 in follicular Non-Hodgkin's Lymphoma patients
R-CVP vs CVP alone: 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%).2
INDICATIONS AND USAGE
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 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
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.
Attention Healthcare Provider: Provide Medication Guide to patient prior to Rituxan infusions.
References
- Data on file, Genentech, Inc.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.
- 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.
