Survival benefits extended to younger patients
MInT* trial: Younger, low-risk DLBCL patients1
Percentages are based on calculations.
*MInT: MabThera® (Rituximab) International Trial.
†CHEMO: Approximately 44% of trial patients in both study arms received CHOEP (CHOP plus etoposide), 49% received CHOP, 4% received MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), and 4% received PMitCEBO (prednisone, mitoxantrone, cyclophosphamide, etoposide, bleomycin, and vincristine).
‡In the MInT trial of younger adults, an age-adjusted IPI was used, which ranged from 0 to 3, and 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. Per the protocol, patients were to have an IPI score of <2.
- In the MInT trial, a Phase III trial, 823 DLBCL patients (ages 18–60 years) were randomized to receive either RITUXAN plus a standard anthracycline-containing chemotherapy regimen (CHEMO) or CHEMO alone as induction therapy3
MInT protocol1: R-CHEMO x6 vs CHEMO x6
- Patients were randomized to receive either 6 three-week cycles of CHEMO plus RITUXAN 375 mg/m2 given on Day 1, or 6 three-week cycles of CHEMO alone3
RITUXAN+CHEMO significantly prolonged survival in younger DLBCL patients2
MInT overall survival (N=823)1,2
- At 2 years, RITUXAN+CHEMO increased OS from 86% to 95% compared with CHEMO alone2
- RITUXAN+CHEMO significantly improved time to treatment failure, the primary study endpoint2
The investigators of the MInT trial observed the following:“The addition of rituximab to six cycles of a CHOP-like chemotherapy improves the outcome of all subgroups of patients with good-prognosis diffuse large-B-cell lymphoma without increased toxic effects.”3Pfreundschuh M et al. Lancet Oncol. 2006;7:379-391.
Most common adverse reactions observed in DLBCL patients age 18–60 years
Skin disorder was the only adverse reaction that was experienced with a >5% higher frequency among patients treated with induction R-CHEMO compared with those treated with induction CHEMO. The incidence of skin disorder was 34.4% (135/393) among CHEMO recipients versus 42.0% (174/414) among R-CHEMO recipients. All of these adverse reactions were Grade 1 or 2 in severity.1
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.
- Pfreundschuh M, Trümper L, Österborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379-391.
