Monoclonal Antibodies

The introduction of monoclonal antibodies has revolutionized the treatment of NHL. Rituximab, a chimeric anti-CD20 antibody, was the first monoclonal antibody approved for cancer treatment. Approximately 50% of patients with relapsed low-grade and follicular lymphomas will respond to treatment with this agent.65 Rituximab also has substantial activity against aggressive lymphomas,66 although it has not been extensively evaluated for transformed lymphomas. In a phase III trial comparing rituximab with 90Y ibritumomab tiuxetan (see below), three of four patients with transformed lymphomas responded to rituximab, alone.67

Rituximab has been combined with EPOCH (etopo-side, prednisone, vincristine, cyclophosphamide, and doxorubicin) to treat 18 patients with transformed B-cell lymphomas in a trial from Switzerland.68 The median event-free survival was 12.4 months.

More recently two anti-CD20 radiolabeled antibodies, 90Y ibritumomab tiuxetan and 131I tositumomab, have been specifically approved for the treatment of transformed B-cell NHL. The overall response rate was 56% in nine patients with transformed B-cell lymphomas who were treated with 90Y ibritumomab tiux-etan.67 At the University of Michigan, the complete response rate was 50% and the overall response rate was 79% for patients with transformed lymphomas following treatment with 131I tositumomab.69 The median progression-free survival was 13.9 months for responders. The outcome was similar for patients with low-grade lymphoma and significantly better than the outcome in patients with de novo aggressive lymphomas who received this treatment (Figure 67.2). The response rate was 39% for 23 patients with transformed lymphomas included in the pivotal trial of 131I tositumomab.70 Patients had received a median of four prior chemotherapy regimens and 48% had bulky disease. The response rate was higher in patients who had transformed to follicular large-cell histology as compared to patients with diffuse histology after transformation. The multicenter trial of 131I tositu-momab included 10 patients with transformed B-cell

Time from treatment (months)

Figure 67.2 Progression-free survival of 59 patients with relapsed or refractory NHL following treatment with 131I tositumomab. (Reprinted from Ref. 69)

Time from treatment (months)

Figure 67.2 Progression-free survival of 59 patients with relapsed or refractory NHL following treatment with 131I tositumomab. (Reprinted from Ref. 69)

lymphoma.71 The complete response rate was 50%, and the overall response rate was 60%. The median response duration was 12.1 months, and these results were similar to other patients with low-grade lymphomas.

The Seattle group used a higher dose of 131I tositumomab followed by autologous stem cell transplantation to treat patients with transformed lymphomas, although individual patient results were not reported.72

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