A Phase II Trial of CHOP Followed by Tositumomab/Iodine-131 Tositumomab for Treatment of Newly Diagnosed Follicular Non-Hodgkin’s Lymphomas (SWOG 9911)

Advanced follicular lymphomas are incurable with conventional chemotherapyregimens. The Southwest Oncology Group (SWOG) investigated the safety andefficacy of a novel treatment approach by administering six cycles of standardCHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar] at 750 mg/m², doxorubicinHCl at 50 mg/m², vincristine [Oncovin] at 1.4 mg/m², and oral prednisone at 100mg for 5 days), given at 3-week intervals, followed by radioimmunotherapy. Fourweeks after completion of the last cycle of CHOP, patients with a partial (PR)or complete remission (CR) to chemotherapy underwent dosimetry with 450 mg ofunlabeled tositumomab (anti-CD20) antibody and 35 mg of trace-labeled iodine-131tositumomab (Bexxar).

Based on the rate of clearance of this dosimetric infusion from the body asassessed by gamma counting, subjects were treated with tositumomab labeled with48 to 115 mCi of iodine-131 (median: 84 mCi), estimated to deliver 75 cGy to thewhole body (or 65 cGy if the platelet count was 100,000 to 149,999/µL). Thistherapeutic dose was administered 1 to 2 weeks after the trace-labeled dose. Atotal of 102 patients with newly diagnosed follicular lymphomas (grade 1, 2, or3) were registered by the time of study closure on June 1, 2000, and 92 wereeligible. Of these, 88 patients are currently evaluable for toxicity from theCHOP regimen and 33 (38%) experienced grade 4 toxicities with CHOP, including 31(35%) with grade 4 hematologic toxicities. Sixty patients are evaluable at thecurrent time for toxicities from iodine-131 tositumomab. Eight patients (13%)had 10 grade 4 toxicities, including 4 with neutropenia, 2 with leukopenia, 2with thrombocytopenia, 1 with an anaphylactoid reaction, and 1 with chest andback pain. There were no treatment-related deaths.

Seventy-one of the currently analyzable patients have been evaluated forresponse to the combination of CHOP plus iodine-131 tositumomab; 51 (80%) haveachieved an objective remission, including 37 confirmed or unconfirmed CRs (52%)and 20 PRs (28%). One patient (1%) had progressive disease on therapy, 2patients (3%) had stable disease, and 11 patients (15%) did not have sufficientdata available to assess response. In 17 patients (24%), the addition ofiodine-131 tositumomab to CHOP improved the overall best response, either from apartial to a complete response (15 patients [21%]) or from an unconfirmed to aconfirmed complete response (2 patients [3%]). Serial molecular monitoring ofthe t(14;18) translocation in the blood and bone marrow was performed bypolymerase chain reaction (PCR) at study entry, after completion of six cyclesof 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 tositumomabradioimmunotherapy 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-131tositumomab regimen to CHOP alone and to CHOP plus rituximab (Rituxan).

Click here to read Dr. Bruce Cheson's commentary on this abstract.