Advanced follicular lymphomas are incurable with conventional chemotherapy regimens. The Southwest Oncology Group (SWOG) investigated the safety and efficacy of a novel treatment approach by administering six cycles of standard CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar] at 750 mg/m², doxorubicin(Drug information on doxorubicin) HCl at 50 mg/m², vincristine [Oncovin] at 1.4 mg/m², and oral prednisone(Drug information on prednisone) at 100 mg for 5 days), given at 3-week intervals, followed by radioimmunotherapy. Four weeks after completion of the last cycle of CHOP, patients with a partial (PR) or complete remission (CR) to chemotherapy underwent dosimetry with 450 mg of unlabeled tositumomab (anti-CD20) antibody and 35 mg of trace-labeled iodine-131 tositumomab (Bexxar).
Based on the rate of clearance of this dosimetric infusion from the body as assessed by gamma counting, subjects were treated with tositumomab labeled with 48 to 115 mCi of iodine-131 (median: 84 mCi), estimated to deliver 75 cGy to the whole body (or 65 cGy if the platelet count was 100,000 to 149,999/µL). This therapeutic dose was administered 1 to 2 weeks after the trace-labeled dose. A total of 102 patients with newly diagnosed follicular lymphomas (grade 1, 2, or 3) were registered by the time of study closure on June 1, 2000, and 92 were eligible. Of these, 88 patients are currently evaluable for toxicity from the CHOP regimen and 33 (38%) experienced grade 4 toxicities with CHOP, including 31 (35%) with grade 4 hematologic toxicities. Sixty patients are evaluable at the current time for toxicities from iodine-131 tositumomab. Eight patients (13%) had 10 grade 4 toxicities, including 4 with neutropenia, 2 with leukopenia, 2 with thrombocytopenia, 1 with an anaphylactoid reaction, and 1 with chest and back pain. There were no treatment-related deaths.
Seventy-one of the currently analyzable patients have been evaluated for response to the combination of CHOP plus iodine-131 tositumomab; 51 (80%) have achieved an objective remission, including 37 confirmed or unconfirmed CRs (52%) and 20 PRs (28%). One patient (1%) had progressive disease on therapy, 2 patients (3%) had stable disease, and 11 patients (15%) did not have sufficient data available to assess response. In 17 patients (24%), the addition of iodine-131 tositumomab to CHOP improved the overall best response, either from a partial to a complete response (15 patients [21%]) or from an unconfirmed to a confirmed complete response (2 patients [3%]). Serial molecular monitoring of the t(14;18) translocation in the blood and bone marrow was performed by polymerase chain reaction (PCR) at study entry, after completion of six cycles of CHOP, and 72 days, 6 months, and 12 months following iodine-131 tositumomab (PCR analysis is currently pending).
CONCLUSION: We conclude that the addition of iodine-131 tositumomab radioimmunotherapy to six cycles of CHOP chemotherapy is feasible, well-tolerated, and efficacious. SWOG has recently initiated a three-armed, prospective randomized study (SWOG 0016) to compare this CHOP plus tositumomab/iodine-131 tositumomab regimen to CHOP alone and to CHOP plus rituximab(Drug information on rituximab) (Rituxan).