Abstract
INTRODUCTION: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) therapy is the standard of care for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, detailed delineation of toxicity data is limited and has not been examined by age. We sought to examine adverse event data in patients receiving R-CHOP from the Cancer and Leukemia Group B (CALGB) 50303 trial to determine if there were differences in grade 3+ toxicities by age cohort or ECOG performance status (PS), and if outcome was impacted by age cohort or toxicity occurrence. MATERIALS AND METHODS: CALGB 50303 was an intergroup phase III study for previously untreated patients with DLBCL that included R-CHOP as one of the trial arms. In the subset of 235 evaluable, seemingly fit patients receiving R-CHOP on this trial, data regarding the occurrence of grade 3+ hematologic and non-hematologic toxicities by treatment arm, as well as completion of protocol therapy, overall response rate (ORR), and survival outcome parameters were collected and analyzed for Alliance A151930. RESULTS: Data were available for further analysis from 235 of 243 patients evaluable for safety, i.e., those who received R-CHOP therapy on this trial, with 165 being <65 years of age, and 70 ≥ 65 years of age. There was an increased rate of grade 3+ non-hematologic (but not hematologic) toxicities in the older age cohorts, after controlling for disease stage and performance status (p < 0.001). One-year and three-year overall survival (OS) were inferior in patients ≥65 years of age, compared to those <65 years of age; there was no difference in one-year or in three-year progression-free survival (PFS) between the age cohorts. DISCUSSION: Standard frontline therapy with R-CHOP can be effectively administered to an older age cohort. We found more grade 3+ non-hematologic, but not hematologic, toxicities in older patients. These data can be used in clinical trial and real-world settings to identify at-risk DLBCL subgroups for which pro-active measures can be utilized to ensure completion of therapy and optimization of clinical outcomes. CLINICALTRIALS: gov Identifier: NCT00118209 (CALGB 50303).