Bartlett NL, et al. - Between 2005 and 2013, 491 subjects were analyzed to assess the clinical outcome with frontline treatment for diffuse large B-cell lymphoma of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). They observed a 2-year PFS progression-free survival (PFS) rate of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP at a median follow-up of 5 years, which was not statistically different between groups. The DA-EPOCH-R arm had more frequent grade 3 and 4 adverse events vs the R-CHOP arm, like infection (16.9% vs 10.7%, respectively), febrile neutropenia (35.0% vs 17.7%, respectively), mucositis (8.4% vs 2.1%, respectively), and neuropathy (18.6% vs 3.3%, respectively). There was no improvement in PFS, OS, or response rate with DA-EPOCH-R vs R-CHOP, in spite of more toxicity and complexity.