NHL Dosing

Established dosing regimens for a variety of treatment settings in NHL

RITUXAN DOSING BY TREATMENT SETTING in NHL1

Chart: RITUXAN DOSING BY TREATMENT SETTING
  • *R-CHEMO: Approximately 75% of patients in both arms of the PRIMA trial received R-CHOP, 22% received R-CVP, and 3% received R-FCM.1
  • †RITUXAN dosing for post-induction setting.
  • NHL=non-Hodgkin's lymphoma; DLBCL=diffuse large B-cell lymphoma; R=RITUXAN; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone; CVP=cyclophosphamide, vincristine, and prednisone; FCM=fludarabine, cyclophosphamide, and mitoxantrone.

Previously untreated follicular, B-cell NHL1

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.

RITUXAN is not recommended for use in patients with severe, active infections.

  • The recommended dose of RITUXAN in combination with chemotherapy is 375 mg/m2 IV infusion, given on Day 1 of each 21-day cycle of CVP‡ chemotherapy, for up to 8 doses

MARCUS (M39021) DOSING SCHEDULE1

Chart: MARCUS (M39021) TREATMENT PROTOCOL: R-CVP ×8
  • ‡CVP=cyclophosphamide 750 mg/m2 on Day 1; vincristine 1.4 mg/m2 on Day 1; prednisolone 40 mg/m2 on Days 1–5.2
  • The recommended dose of RITUXAN in patients achieving a complete or partial response to R-CHEMO is 375 mg/m2 IV infusion, given 8 weeks after the completion of induction therapy, every 2 months for up to 12 doses

PRIMA DOSING SCHEDULE1

Chart: PRIMA TREATMENT PROTOCOL
  • §R-CHEMO: Approximately 75% of patients in both arms of the PRIMA trial received R-CHOP, 22% received R-CVP, and 3% received R-FCM.1
  • ||CRu=complete response, unconfirmed, defined as the following: a) disappearance of all detectable evidence of disease as well as disease-related symptoms and normalization of NHL-related biochemical abnormalities, b) reduction in size of enlarged organs palpable on physical examination in addition to the following features: i) regression of lymph node (greater than 1.5 cm in its greatest transverse diameter) by more than 75% in sum of the products of the greatest diameters and/or ii) indeterminate bone marrow.3
  • PRIMA=Primary RItuximab and MAintenance; PR=partial response; CR=complete response.

Non-progressing, low-grade, B-cell NHL1

Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL, as a single agent, after first-line CVP chemotherapy.

RITUXAN is not recommended for use in patients with severe, active infections.

  • The recommended dose of RITUXAN in patients who have not progressed following 6 to 8 twenty-one-day cycles of CVP chemotherapy is 375 mg/m2 IV infusion once weekly for 4 weeks, every 6 months, for up to 16 doses

ECOG 1496 DOSING SCHEDULE1

Chart: ECOG 1496 TREATMENT PROTOCOL: <br />16 DOSES OF RITUXAN FOLLOWING CVP
  • CVP=cyclophosphamide 1 g/m2 on Day 1; vincristine 1.4 mg/m2 on Day 1; prednisone 100 mg/m2 on Days 1–5. After the completion of 6 to 8 twenty-one–day cycles of CVP, patients achieving a CR, PR, or SD were randomized to receive no further treatment or to receive post-induction therapy with RITUXAN. Beginning 4 weeks after completion of induction therapy, patients randomized to RITUXAN received 1 cycle of 4 weekly treatments with 375 mg/m2 RITUXAN, every 6 months for up to 4 cycles.4
  • ECOG=Eastern Cooperative Oncology Group; IWF=International Working Formulation; SD=stable disease; PFS=progression-free survival.

Relapsed or refractory, low-grade or follicular, B-cell NHL1

Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.

RITUXAN is not recommended for use in patients with severe, active infections.

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion once weekly for 4 or 8 doses

McLAUGHLIN AND PIRO DOSING SCHEDULES1

Chart: McLAUGHLIN WEEKLY ×4 AND PIRO WEEKLY ×8 TREATMENT PROTOCOL

Retreatment therapy

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion once weekly for 4 doses in patients who develop progressive disease after previous RITUXAN therapy

Diffuse large B-cell NHL (DLBCL)1

Previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens.

RITUXAN is not recommended for use in patients with severe, active infections.

  • The recommended dose of RITUXAN is 375 mg/m2 IV infusion given on Day 1 of each 21-day cycle of CHOP# or other anthracycline-based chemotherapy regimens, for up to 8 infusions

GELA DOSING SCHEDULE1

Chart: TREATMENT PROTOCOL FROM GELA: R-CHOP ×8
  • #CHOP=cyclophosphamide 750 mg/m2 on Day 1, doxorubicin 50 mg/m2 on Day 1, vincristine 1.4 mg/m2 on Day 1; prednisone 40 mg/m2/day on Days 1–5.5
  • GELA=Groupe d'Etude des Lymphomes de l'Adulte.

Infusion reactions

  • RITUXAN can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion, with time to onset of 30 to 120 minutes
  • RITUXAN-induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death
  • Premedicate patients with an antihistamine and acetaminophen prior to dosing. Depending on the severity of the infusion reaction and the required interventions, slow the infusion rate, interrupt the infusion, or permanently discontinue RITUXAN
  • Closely monitor patients with pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells (≥25,000/mm3)

References:
  1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2011.
  2. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105:1417-1423.
  3. Data on file, Genentech, Inc.
  4. Hochster H, Weller E, Gascoyne RD, et al. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG 1496 study. J Clin Oncol. 2009;27:1607-1614.
  5. Coiffier B, Lepage E, Brière J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235-242.

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
  • •  Weekly ×4  •  Weekly ×8  •  Bulky disease  •  Retreatment
  • 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 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 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 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.