RITUXAN+CHEMO significantly prolonged OS in younger DLBCL patients
MInT TRIAL DESIGN: R-CHEMO ×6 VS CHEMO ×61
- CHEMO=CHOP every 3 weeks, CHOEP (CHOP+etoposide) every 3 weeks, MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin) biweekly, or PMitCEBO (prednisolone, mitoxantrone, cyclophosphamide, etoposide, bleomycin, and vincristine) biweekly. R=RITUXAN 375 mg/m2 every 3 weeks for 6 cycles, beginning on the first day of chemotherapy.2
- MInT=MabThera® (Rituximab) International Trial; OS=overall survival; DLBCL=diffuse large B-cell lymphoma; IPI=International Prognostic Index; CHOP=cyclophosphamide, doxorubicin, vincristine, and prednisone.
MInT: YOUNGER, LOW-RISK DLBCL PATIENTS1
|Baseline patient characteristics||
|Age range (years)||18-60||18-60|
|Elevated LDH (>1×ULN)||30%||29%|
|Ann Arbor Stage||I/II III/IV||
|ECOG performance status||0-1 2-3||
|Bulky disease (>10 cm)||50%||48%|
|Extranodal involvement (≥2)||33%||35%|
|IPI score*||<2 ≥2||
- *In the MInT trial of younger adults, an age-adjusted IPI was used, which ranged from 0 to 3 and was derived by assigning 1 point for each of the following risk factors: Ann Arbor Stage III or IV, ECOG performance status ≥2, and elevated LDH. Per the protocol, patients were to have an IPI score of <2.
- LDH=lactate dehydrogenase; ULN=upper limit of normal; ECOG=Eastern Cooperative Oncology Group.
R-CHEMO provided a significant overall survival advantage in DLBCL
- 1.8-year OS was 95% for R-CHEMO vs 86% for CHEMO alone (p<0.05)3
- Significant improvement in the primary endpoint of time to treatment failure at 1.8-year follow-up (55% risk reduction, p<0.05)3
Safety for RITUXAN in combination with CHOP chemotherapy for DLBCL
- Detailed safety data collection in these trials was primarily limited to Grade 3 and 4 adverse reactions and serious reactions. In studies of elderly patients with DLBCL, the following adverse reactions, regardless of severity, were reported more frequently (≥5%) in patients ≥60 years of age receiving R-CHOP as compared with CHOP alone: pyrexia (56% vs 46%), lung disorder (31% vs 24%), cardiac disorder (29% vs 21%), and chills (13% vs 4%)
- In one of the studies of elderly patients, GELA LNH 98-5, 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)
- Data on file, Genentech, Inc.
- Pfreundschuh M, Trümper L, Österborg A, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379-391.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012.
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.