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

Chart: Overall PFS Improvement
  • *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%)

References:
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012.
  2. Data on file, Genentech, Inc.

Indications

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

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 infusion.