Davis Bulky Disease Trial (Weekly ×4)
RITUXAN monotherapy demonstrated benefit in heavily pretreated, bulky disease NHL patients
DAVIS BULKY DISEASE TRIAL DESIGN1
- Treatment in the trial consisted of RITUXAN 375 mg/m2 administered once weekly intravenously for a total of 4 infusions. Patients were required to have either failed to respond to primary chemotherapy or to have relapsed after chemotherapy. Patients had received up to 13 prior regimens (median: 3).1
- NHL=non-Hodgkin's lymphoma.
DAVIS BULKY DISEASE TRIAL: HEAVILY PRETREATED LOW-GRADE OR FOLLICULAR NHL1
|Patient characteristics||No. of patients (%)|
|Age range (years)||33-79|
|Histologic grade*||Low (IWF A, B, or C) Intermediate (IWF D)||
|Disease stage||I/II III/IV Unknown||
- *Based on the International Working Formulation (IWF).
- A response rate of 36% (3% CR, 33% PR) was achieved in these bulky disease patients2
- CR=complete response; PR=partial response.
Single-agent RITUXAN for relapsed or refractory, low-grade or follicular NHL
- Grade 3 and 4 cytopenias were reported in 48% of patients and included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). Serious Grade 3 or 4 infections, including sepsis, occurred in <5% of patients
- The overall incidence of infections was 31%: bacterial (19%), viral (10%), unknown (6%), and fungal (1%)
- Davis TA, White CA, Grillo-López AJ, et al. Single-agent monoclonal antibody efficacy in bulky non-Hodgkin’s lymphoma: results of a phase II trial of rituximab. J Clin Oncol. 1999;17:1851-1857.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2013.
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, SEVERE MUCOCUTANEOUS REACTIONS, HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
- 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. Monitor patients closely. Discontinue RITUXAN infusion for severe reactions and provide medical treatment for Grade 3 or 4 infusion reactions
- Severe Mucocutaneous Reactions: Severe, including fatal, mucocutaneous reactions can occur in patients receiving RITUXAN
- Hepatitis B Virus (HBV) Reactivation: HBV reactivation can occur in patients treated with RITUXAN, in some cases resulting in fulminant hepatitis, hepatic failure, and death. Screen all patients for HBV infection before treatment initiation, and monitor patients during and after treatment with RITUXAN. Discontinue RITUXAN and concomitant medications in the event of HBV reactivation
- Progressive Multifocal Leukoencephalopathy (PML), including fatal PML, can occur in patients receiving RITUXAN
Warnings and Precautions
Tumor Lysis Syndrome
- Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12−24 hours after the first infusion of RITUXAN in patients with NHL. A high number of circulating malignant cells (≥25,000/mm3) or high tumor burden, confers a greater risk of TLS. Administer aggressive intravenous hydration and anti hyperuricemic therapy in patients at high risk for TLS
- Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of RITUXAN-based therapy. Discontinue RITUXAN for serious infections and institute appropriate anti infective therapy
- Discontinue infusions for serious or life threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of RITUXAN for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina
- Severe, including fatal, renal toxicity can occur after RITUXAN administration in patients with NHL. Monitor closely for signs of renal failure and discontinue RITUXAN in patients with a rising serum creatinine or oliguria
Bowel Obstruction and Perforation
- Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving RITUXAN in combination with chemotherapy. Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur
- The safety of immunization with live viral vaccines following RITUXAN therapy has not been studied and vaccination with live virus vaccines is not recommended
- Obtain complete blood counts (CBC) prior to each RITUXAN course
Additional Important Safety Information
- The most common Grade 3 or 4 adverse reactions in clinical trials of NHL and CLL were infusion reactions, neutropenia, leukopenia, anemia, thrombocytopenia, and infections. Additionally, lymphopenia and lung disorder were seen in NHL trials; and febrile neutropenia, pancytopenia, hypotension, and hepatitis B were seen in CLL trials
- The most common adverse reactions (incidence ≥25%) in clinical trials of NHL and CLL were infusion reactions. Additionally, fever, lymphopenia, chills, infection, and asthenia were seen in NHL trials; and neutropenia was seen in CLL trials
- Pregnancy: Category C. There are no adequate and well-controlled studies of rituximab in pregnant women
Attention Healthcare Provider: Provide Medication Guide to patient prior to RITUXAN infusion.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.