Rituximab Treatment Failures: Tositumomab and Iodine I-131 Tositumomab (Bexxar) Can Produce Meaningful Durable Responses
Reviewer: Walter Sall, MD
Last Modified: December 7, 2002
Presenter: Sandra J. Horning Presenter's Affiliation: Stanford University Type of Session: Poster
Rituxan is a chimeric monoclonal antibody (MAb)directed against the CD20 cell surface protein.
It effected a 50% overall response rate in the pivotal trial treating relapsed or refractory indolent non-Hodgkin's lymphoma (NHL). Unfortunately, response duration is usually short (mean 11.6 months) and most patients need additional therapy.
Bexxar (Iodine I-131 Tositumomab) is a radiolabelled murine MAb with a similar response rate in NHL and median response duration > one year. Antibody mediated cytotoxicity and targeted radiation from I-131 combine to produce Bexxar's activity.
Materials and Methods
Phase II multicenter trial of Bexxar in patients with indolent or transformed indolent NHL who have progressed after previous Rituxan therapy.
40 patients enrolled between July 1998 and November 1999. 24 had no response to rituxan, 12 had progression after less than 6 months and 4 had progression after more than 6 months. Median response duration was 4.7 months.
Median follow-up was 25.6 months. 30% of patients had marrow involvement and 31% had elevated LDH. Median age of patients was 57 years and median number of prior treatment regimens was 4.
The standard Bexxar treatment protocol (described elsewhere) was followed in this trial. Initially, a dosimetric dose was given in order to determine the therapeutic dose required to provide 75cGy of total body radiation. This dose was provided in a single administration.
Overall response rate was 68% with a median response duration of 14.7 months. Complete response rate was 30%.
Median time to progression was 12.2 months. At last analysis, 22.5% of patients had maintained a complete response.
67% of patients who had no response to rituxan, did respond to Bexxar.
Bexxar is highly effective in relapsed and refractory indolent and transformed lymphoma which has progressed following rituxan therapy.
A significant number of patients attain durable responses of greater than one year.
A significant percentage of heavily pretreated patients achieving a CR sustain their response for more than one year (43%).
Duration of Bexxar response is longer than response to prior rituxan.
Heavily pretreated indolent NHL patients who have failed treatment with rituxan can have a durable response to Bexxar. In fact, patients had a longer response to Bexxar than they had to their prior rituxan therapy. This despite the fact that Bexxar and rituxan have the identical molecular target. This trial shows the efficacy and low toxicity of Bexxar in refractory indolent NHL. Further investigations into its use in these patients and its sequencing with other novel treatment modalities is justified by the data presented.
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