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U.S. Department of Health and Human Services

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FDA approves rituximab (Rituxan) for use in the first‑line treatment of patients with diffuse large B-cell, CD20‑positive, non-Hodgkin's lymphoma in combination with CHOP or other anthracycline‑based chemotherapy regimens

On February 10, 2006, the U.S. Food and Drug Administration granted approval to rituximab (Rituxan, Genentech and Biogen-Idec) for use in the first‑line treatment of patients with diffuse large B-cell, CD20‑positive, non-Hodgkin's lymphoma in combination with CHOP or other anthracycline‑based chemotherapy regimens.

Safety and efficacy were demonstrated in three randomized, active-controlled, open-label, multicenter studies with a collective enrollment of 1854 patients. These trials enrolled primarily patients with diffuse large B-cell lymphoma who had not received prior therapy. Two of the three studies (E4494 and LNH 98-5/GELA) were restricted to patients 60 years of age or greater, while the third (M39045/MiNT) enrolled patients between ages 18 and 60 years. In E4494 and LNH98-5, the majority of patients had Stage 3-4 disease, while the majority had stage 1-2 disease in M39045. Patients received rituximab 375 mg/m2 by differing schedules in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or other anthracycline‑based chemotherapy regimens (R-CHEMO). Each study utilized composite time-to-event endpoints, incorporating disease progression events as the main outcome measure and included overall survival among secondary analyses. Determination of the primary endpoint was based upon investigator-assessment.

In each study, hazard ratios for the main outcome measures favored the rituximab-containing arms. In addition, each study showed an overall survival benefit among patients receiving rituximab. With two years of follow-up, more patients were alive by Kaplan-Meier estimates in the rituximab-containing versus control arms for each study as follows: 74% vs. 63%, 69% vs. 58%, and 95% vs. 86%. In one of the studies, 5-year data were available and demonstrated that the survival advantage persisted with estimated 5-year survival rates of 58% vs. 46% for R-CHOP and CHOP, respectively. Results were generally consistent across subgroups, including age, gender and disease prognostic variables. There was neither additional improvement in progression-free survival nor overall survival for patients in E4494 receiving R-CHOP who were subsequently randomized to additional rituximab after achieving a complete or partial response as compared to those who received R-CHOP alone.

In all three studies, the dose intensity for rituximab in the R-CHOP and R-CHEMO induction arms was high and rituximab treatment was not associated with a reduction in the dose intensities of individual chemotherapy components. Adverse events associated with rituximab were generally consistent with the labeled adverse reactions described for single-agent rituximab. Grade 3/ 4 adverse events occurring with ≥ 2% excess in the rituximab arm in at least one study included infection, thrombocytopenia and lung toxicity/dyspnea. The following serious adverse reactions, some with fatal outcomes, have been reported in patients receiving rituximab: severe or fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, hepatitis B reactivation with fulminant hepatitis, other viral infections, hypersensitivity reactions, cardiac arrhythmias, renal toxicity, and bowel obstruction and perforation.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at Drugs@FDA 

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System by phone at 1-800-FDA-1088; by facsimile 1-800-FDA-0178 by mail using the Form 3500