Weekly x4 Trial (McLaughlin Trial)
Single-agent RITUXAN delivered durable responses
Original pivotal trial: Heavily pretreated low-grade or follicular NHL2
*Subset analyses conducted on the assessable group of 151 patients; results for the intent-to-treat group were virtually identical.
- In the original multicenter pivotal trial of 166 patients receiving RITUXAN 375 mg/m2 weekly for 4 doses, the complete response (CR) rate was 6%, the partial response (PR) rate was 42%, and the overall response rate (ORR) was 48%1
Durable responses achieved despite a median of 3 prior therapies (range 1–10)2
Median duration of response: Pivotal trial (n=80)1
- Prior therapy included chemotherapy in 97%, radiotherapy in 25%, and bone marrow or peripheral-blood stem-cell transplantation in 14% of patients2
Grade 3–4 adverse reactions in patients receiving single-agent RITUXAN
The most common Grade 3 or 4 adverse events that occurred more frequently (>5%) in patients receiving single-agent RITUXAN were lymphopenia (40%), neutropenia (6%), leukopenia (4%), and infection (4%).1
Tumor reduction in heavily pretreated patients3
Reduction in lesion size (N=166)3
- In the pivotal trial, even some patients who had stable or nonresponsive disease benefited from RITUXAN therapy4
RITUXAN serum levels were higher in responders5
Median RITUXAN serum levels throughout and following treatment5
- At all time points in the pivotal trial, the median serum level was higher in patients who had achieved a clinical response to treatment than in nonresponders5
“The high response rate with this antibody was encouraging, including its efficacy in patients with adverse prognostic features, such as high LDH or β2-microglobulin levels, and in patients who often tolerate standard therapies poorly.”2McLaughlin P et al. J Clin Oncol. 1998;16:2825-2833.
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
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2008.
- McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-2833.
- Kunkel L,Wong A, Maneatis T, et al. Optimizing the use of rituximab for the treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Semin Oncol. 2000;27(suppl 12):53-61.
- McLaughlin P, Hagemeister FB, Grillo-López AJ. Rituximab in indolent lymphoma: the single-agent pivotal trial. Semin Oncol. 1999;26(suppl 14):79-87.
- Berinstein NL, Grillo-López AJ, White CA, et al. Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin's lymphoma. Ann Oncol. 1998;9:995-1001.
