R-CHOP with Iodine-131 Tositumomab Consolidation for Advanced Stage Diffuse Large B-Cell Lymphoma (DLBCL): Southwest Oncology Group Protocol S0433

Although the majority of patients (pts) with DLBCL have durable remissions following R-CHOP chemotherapy, a substantial proportion of pts with advanced stage disease and other clinical risk factors are not cured. Low toxicity options are required for the majority of pts who are over age 60, or have medical comorbidities. Radioimmunotherapy, a low-toxicity option, is active in relapsed DLBCL (Blood 110:54), and improves PFS when used as consolidation after chemotherapy in follicular lymphoma (JCO 26:5156). We therefore evaluated consolidative radioimmunotherapy with iodine-131 tositumomab in pts with previously untreated DLBCL.

Eligible pts had bulky stage II, or advanced stage DLBCL with measurable disease and adequate organ function. Treatment was 6 cycles of R-CHOP-21, followed by 2 cycles of CHOP-21 (no rituximab), followed by iodine-131 tositumomab (65 cGy if platelet count between 100 and 150/mm³ or 75 cGy if normal platelet count) 4–12 weeks after last dose of CHOP.

Eighty six pts (84 eligible; 45 females) were enrolled. Median age was 64 years; International Prognostic Index risks were low (n=20, 24%), low intermediate (n=27; 32%), high intermediate (n=27, 32%) and high (n=10, 12%). Five pts died of toxicities possibly related to therapy including one case each of febrile neutropenia, acute myeloid leukemia, and renal failure; there were two deaths from cardiac ischemia including one following a GI bleed in setting of thrombocytopenia after iodine-131 tositumomab. With a median follow-up of 12 months, 26 pts have progressed or died, with a 1-year progression-free survival (PFS) estimate of 75% (95%CI: 64%-85%), and 1-year overall survival (OS) estimate of 83% (95% CI:74%-93%). Based on prior studies, the estimated historical 1-year PFS rate with R-CHOP alone in this population is 74%. Complete data on iodine-131 tositumomab treatment is available for 73 of 84 eligible patients: 23 pts (32%) did not receive iodine-131 tositumomab due to early progression (n=3), other adverse event (n=6), refusal (n=6), death (n=3), or other reasons (n=5).

A consolidation strategy utilizing iodine-131 tositumomab after 8 cycles of CHOP chemotherapy (6 with rituximab) for DLBCL does not appear to be promising in regard to 1 year PFS or OS. Unlike follicular lymphoma, in this population of DLBCL, early progressions, deaths, and declining performance status during CHOP chemotherapy limits the number of pts who ultimately can benefit from a planned consolidation approach. These current results suggest that the incorporation of novel agents earlier in therapy may ultimately have greater impact in DLBCL than consolidation or maintenance approaches. (Supported by 5U10CA32102-31, 5U10CA38926-25, and GlaxoSmithKline).

Friedberg:Genentech: Honoraria. Off Label Use: Iodine-131 tositumomab for large cell lymphoma. Gopal:GlaxoSmithKline: Research Funding. Press:Trubion Pharmaceuticals: Consultancy, Equity Ownership; PhaseRx: Equity Ownership; Algeta: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Genentech: Honoraria; Spectrum: Honoraria.