R-CHOP

R-CHOP showed improved event-free survival (EFS) and OS compared with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) alone in 399 patients older than 60 years with advanced-stage DLBCL (EFS rate, 57% vs. 38%; P = .002, and OS rate, 70% vs. 57%; P = .007 at 2 years).[7][Level of evidence A1] At a median follow-up of 10 years, the OS rate of patients who received R-CHOP was 44% compared with 28% for patients who received CHOP (P < .0001).[8]

Similarly, for 326 evaluable patients younger than 61 years, R-CHOP showed improved EFS and OS compared with CHOP alone (EFS rate, 79% vs. 59%, P = .001, and OS rate, 93% vs. 84%, P = .001 at 3 years).[9][Level of evidence A1]

A randomized study (DSHNHL-1999-1A [NCT00052936]) of 1,222 patients older than 60 years compared R-CHOP given every 2 weeks for six or eight cycles with CHOP given every 2 weeks for six or eight cycles.[10] With a median follow-up of 72 months, the EFS favored R-CHOP given every 2 weeks for six or eight cycles (6-year EFS rate, 74% vs. 56%; P < .0001). The OS favored R-CHOP for only six cycles because of increased toxicity in the eight-cycle arm (6-year OS rate, 90% vs. 80%; P = .0004).[10][Level of evidence A1] There was no comparison with standard R-CHOP or CHOP given every 3 weeks.

A trial (NCT00140595) of 380 patients younger than 60 years with DLBCL and an age-adjusted IPI score of 1 randomly assigned patients to receive ACVBP and R-ACVBP plus consolidation with methotrexate, ifosfamide, etoposide, and cytarabine versus CHOP and rituximab.[11] With a median follow-up of 44 months, 3-year OS rates favored R-ACVBP (92% vs. 84%; HR, 0.44; 95% CI, 0.28–0.81, P = .007).[11][Level of evidence A1] The significantly worse toxicities with R-ACVBP, the narrow target population (<60 years with either elevated lactate dehydrogenase [LDH] or stage III-stage IV disease, but not both), and the lack of a confirmatory trial may inhibit adoption of R-ACVBP as a new standard of care.[12]