In case the link disappears, here's the executive summary. The full report is available at the source. bcbs.com
<Rituximab for Treatment of Intermediate and Aggressive B-cell Non-Hodgkin’s Lymphomas
Assessment Program
Volume 17, No. 3
June 2002
Executive Summary
Rituximab is a recombinant, humanized monoclonal antibody directed against the CD20 antigen, a cell surface molecule expressed by B-lymphocytes and B-cell malignancies. In a prior Technology Evaluation Center (TEC) Assessment (Vol. 16, No. 7; 2001), the Blue Cross and Blue Shield Association Medical Advisory Panel concluded that use of rituximab for patients with intermediate grade or aggressive non-Hodgkin’s lymphoma (NHL) did not meet the TEC criteria. The earlier Assessment’s Review of Evidence summarized preliminary results from a randomized controlled trial that compared combination chemotherapy alone to the same combination plus rituximab for patients with diffuse large B-cell lymphoma (the most common type of intermediate/aggressive NHL). At that time, however, these results were available only in meeting abstracts and had not yet been published in a peer-reviewed journal. This randomized trial recently was published in full. Consequently, the objective of this Assessment is to update the Assessment conclusions on the use of rituximab for patients with intermediate or aggressive B-cell NHL.
Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether use of rituximab to treat patients with intermediate or aggressive B-cell NHL meets the TEC criteria.
1. The technology must have final approval from the appropriate governmental regulatory bodies.
On November 26, 1997, Genentech, Inc. received approval from the U.S. Food and Drug Administration (FDA) for its biologics license application to market rituximab (Rituxan®). Genentech Inc. prepares rituximab for clinical use from formulated bulk preparations manufactured by IDEC Pharmaceuticals Corporation under a separate biologics license. In each biologics license, rituximab is indicated for the treatment of patients with relapsed or refractory low-grade or follicular, B-cell non-Hodgkin’s lymphoma. Thus, use of rituximab for intermediate or aggressive NHL represents an off-label use of an approved drug.
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.
Data were available from a randomized, controlled, multicenter trial comparing rituximab plus combination chemotherapy using CHOP (n=202) to CHOP alone (n=197) in previously untreated elderly patients with diffuse large B-cell lymphoma, the most common type of intermediate/ aggressive B-cell NHL. Limited additional evidence was available from 3 uncontrolled studies (combined n=115). This evidence is sufficient to permit conclusions on the outcomes of rituximab therapy for patients with intermediate/aggressive B-cell NHL.
3. The technology must improve the net health outcome; and
4. The technology must be as beneficial as any established alternatives.
In the randomized trial on patients with diffuse large B-cell lymphoma, there were 86 events (progression, relapse, or death) in the CHOP+rituximab arm and 120 events in the CHOP-only arm at 24 months’ median follow-up. By intent-to-treat analysis, median event-free survival was not reached at 3 years in the experimental arm and was 13 months in the control arm (p<0.001). Event-free survival at 2 years (95% CI) was 57% (50-64%) in the CHOP+rituximab arm and 38% (32-45%) in the CHOP-alone arm (relative risk 0.58; 95% CI, 0.44-0.77). Median overall survival was not reached in either arm. However, 59 patients (29%) in the CHOP+rituximab arm died, and 81 (41%) died in the CHOP alone arm (relative risk, 0.64; 95% CI, 0.45-0.89; p=0.007). Survival at 2 years (95% CI) was 70% (63-77%) in the CHOP+rituximab arm and 57% (50-64%) in the CHOP alone arm. Investigators reported approximately the same incidence of clinically relevant toxicity in each study arm.
Data from 3 uncontrolled studies confirmed the high response rates to rituximab reported from the randomized trial. However, the uncontrolled studies did not report survival or event-free survival. Nevertheless, evidence from the randomized trial is sufficient to permit the conclusion that rituximab improves health outcomes of patients with other intermediate or aggressive NHL and is as beneficial as any established alternatives.
5. The improvement must be attainable outside the investigational settings.
The outcomes reported from the randomized trial comparing CHOP+rituximab to CHOP alone are attainable at institutions with experience managing the side effects of combination chemotherapy in patients with other intermediate or aggressive NHL.
Based on the above, use of rituximab meets the TEC criteria to treat patients with intermediate or aggressive B-cell non-Hodgkin’s lymphomas. >
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