Phase II study of dose-adjusted EPOCH-R in untreated de novo CD20+ diffuse large B-cell lymphoma (DLBCL)-CALGB 50103.

6530 Background: DA-EPOCH-R is a rationally designed regimen based on schedule optimization and pharmacodynamic dosing. Studies suggest it overcomes adverse effects of tumor proliferation and bcl-2 in de novo DLBCL and adjusts for differences in patient drug clearance. An NCI study in 83 untreated de novo DLBCL patients shows a PFS and OS of 82% at 32 months median follow-up and no relapses beyond 2 years. PFS is 94% for low (0-2) and 57% for high (3-5) IPI at 3 years. Hence, CALGB undertook a confirmatory phase II study. METHODS: Eligibility: untreated de novo CD20+ DLBCL; ≥ 18 years; stage II-IV; ECOG PS 0-2; and adequate organ function unless due to disease. Patients received DA-EPOCH-R + filgrastim for 6-8 cycles, based on response, and no patients received radiation. Endpoints were PFS, OS and toxicity. Study design is a cooperative group prospective phase II. RESULTS: Of 78 patients, 5 were ineligible. Patient characteristics are median age (range) 58 (23-80) years, and IPI of low (0-2) in 60% and high (3-5) in 40% of patients. Treatment was administered in 18 centers and toxicity assessed in 72 patients. The pharmacodynamic endpoint of grade 4 neutropenia occurred in 96% of patients. Febrile neutropenia occurred in 33% of patients. Grade 4 anemia and thrombocytopenia occurred in 11% and 15% of patients, respectively. Gastrointestinal, thrombosis or neurological toxicities were rare at grade 4 (0-3%) and infrequent at grade 3 (0-14%). No patients had cardiac failure and there was one treatment associated death from CNS hemorrhage. Ninety percent of patients completed at least 6 cycles and 20% received 8 cycles. ORR was 100% with 68% CR and 32% PR. With a median (range) follow-up of 11 (2.4-22.8) months, 10 patients progressed (8 in the first year) with similar rates in CR's (6/49) and PR's (4/23). At 18 months, PFS is 80% overall, and 93% and 46%, respectively, in low (0-2) and high (3-5) IPI. Survival is 88% at 18 months. CONCLUSIONS: DA-EPOCH-R can be administered in a cooperative group with acceptable toxicity. Preliminary survival results are encouraging and consistent with the NCI study. A CALGB randomized phase III study of DA-EPOCH-R versus R-CHOP with microarray tumor analysis will begin early next year. [Table: see text].

Duke Scholars

Author Donna Niedzwiecki Biostatistics & Bioinformatics, Division of Biostatistics