An Update of a Phase II Trial of CHOP Followed by Tositumomab/Iodine I-131 Tositumomab (Bexxar®) for Front-Line Treatment of Advanced Stage, Follicular Lymphoma: Southwest Oncology Group Protocol 9911.

Advanced follicular lymphomas (FL) are incurable with conventional chemotherapy regimens. The Southwest Oncology Group investigated the safety and efficacy of a novel treatment for FL by administering 6 cycles of CHOP chemotherapy followed by radioimmunotherapy (RIT) with tositumomab/iodine I-131 tositumomab. Patients were eligible if they had advanced stage (bulky stage II, III or IV) evaluable FL of any grade (1, 2, or 3) and had not received any prior therapy. Patients received 6 cycles of CHOP (750 mg/m² cyclophosphamide, 50 mg/m² doxorubicin, 1.4 mg/m² vincristine, and 100 mg prednisone daily for 5 days) at 3 week intervals. Patients achieving a PR or CR were eligible to proceed to RIT with 450 mg tositumomab antibody followed by a trace-labeled infusion of 35 mg of I-131-tositumomab (5 mCi). Serial gamma camera imaging was done on 3 occasions over the next week to determine the rate of clearance of the I-131-tositumomab. Subjects were treated 1–2 weeks later with 450 mg tositumomab antibody followed by a therapeutic infusion of 35 mg of I-131-tositumomab labeled with sufficient I-131 (48–115 mCi) to deliver a total body dose of 75 cGy. 102 patients were entered between May 15, 1999 and June 1, 2000, 90 were eligible, and 84 received Bexxar. Of the 90 eligible subjects, 98% were white, 61% male, 27% had B symptoms, 60% were grade 1, 29% grade 2, 11% grade 3, 23% had masses >10 cm, and 62% were stage IV. Toxicities were moderate (presented at ASH 2003). There were no treatment-related deaths. Of 89 patients evaluable for CHOP toxicities, 39% had at worst grade 4 events and 35% at worst grade 3 events, primarily neutropenia. Of 81 patients evaluable for RIT toxicities, 12% had at worst grade 4 and 35% at worst grade 3 toxicities, primarily leukopenia, neutropenia and thrombocytopenia. Grade 3–4 non-hematologic toxicities were uncommon. Of the 90 eligible patients, 6 (7%) had insufficient documentation to assess response, 62 (69%) achieved complete remissions (CR or CRu), 20 (22%) had a partial response (PR), and 2 (2%) had stable disease. If response analysis is limited to the 84 patients for whom sufficient documentation is available to assess response, 98% had objective remissions, including 74% with complete remission (CR or CRu) and 24% with partial remissions (PR). The 4 yr progression-free survival (PFS) and 4 yr overall survival (OS) are listed below compared to prior SWOG studies using CHOP without antibodies:

These observations suggest that CHOP followed by tositumomab/I-131 tositumomab is an attractive approach for FL that may improve the outcome of the disease. This pilot study forms the basis for the current randomized Phase III Intergroup Trial comparing CHOP followed by Bexxar to CHOP with 6 doses of rituximab (SWOG 0016/CALG 50102).