Post-induction Therapy for Low-grade or Follicular NHL
RITUXAN after first-line induction nearly doubled overall PFS, as shown in 2 large Phase III trials in low-grade/follicular NHL
OVERALL PFS IMPROVEMENT1,2
- *R-CHEMO: Approximately 75% of trial patients in both trial arms received R-CHOP, 22% received R-CVP, and 3% received R-FCM.1
- †In both trials, improvement in overall PFS was calculated using the formula (1–HR)/HR. In the ECOG 1496 trial, PFS improvement is based on the HR of 0.49 found in the prescribing information.
- NHL=non-Hodgkin's lymphoma; PFS=progression-free survival; HR=hazard ratio; R=RITUXAN; PRIMA=Primary RItuximab and MAintenance; CVP=cyclophosphamide, vincristine, and prednisone; ECOG=Eastern Cooperative Oncology Group; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; FCM=fludarabine, cyclophosphamide, and mitoxantrone.
RITUXAN after R-CHEMO in the PRIMA trial1,2
- Patients with advanced follicular NHL were randomized to receive either RITUXAN or no further therapy if they achieved a CR, CRu, or PR with R-CHEMO induction therapy
- At 2-year median follow-up, there was a 46% reduction in the risk of progression, relapse, or death with RITUXAN vs observation (p<0.0001)
- RITUXAN following R-CHEMO nearly doubled the likelihood of remaining progression-free vs observation
- CR=complete response; CRu=complete response, unconfirmed; PR=partial response.
RITUXAN after CVP in the ECOG 1496 trial1,2
- Patients with advanced low-grade NHL were randomized to receive either RITUXAN or no further therapy if they achieved a CR, PR, or SD with CVP induction therapy
- At 2.3-year median follow-up, there was a 51% reduction in the risk of relapse, progression, or death with RITUXAN vs observation (p≤0.05)
- RITUXAN following CVP more than doubled the likelihood of remaining progression-free vs observation
- SD=stable disease.
Safety for single-agent RITUXAN as maintenance for follicular NHL after first-line RITUXAN-based chemotherapy
- Detailed safety data collection was limited to Grade ≥2 infections, Grade ≥3 adverse reactions, and serious adverse reactions
- The most frequently reported adverse reaction was infections. In patients receiving RITUXAN as single-agent maintenance therapy following RITUXAN plus chemotherapy, infections were reported more frequently compared with the observation arm (37% vs 22%). Most infections reported with RITUXAN maintenance were Grade 2
- The most common Grade 3-4 adverse reactions occurring at a higher incidence (≥2%) in the RITUXAN arm than in the observation arm were infections (4% vs 1%) and neutropenia (4% vs <1%)
Safety for 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® (Rituximab) full prescribing information, Genentech, Inc., 2012.
- Data on file, Genentech, Inc.
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
Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.