Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review

Abstract

The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone+rituximab) is often faced by clinicians. We conducted a systematic review assessing the impact of R-CHOP DI on DLBCL survival outcomes, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P) guidelines. We searched MEDLINE, EMBASE, and Cochrane CENTRAL for studies with ≥100 patients treated with R-CHOP/R-CHOP–like therapies published from January 2002 through November 2020. Studies were included if they reported the impact of R-CHOP DI on survival outcomes. We screened records, extracted data, and reviewed all the studies for quality and statistical appraisal. Of 380 screened records, 13 studies including 5188 patients were reviewed. DI was often calculated as the ratio of the cumulative delivered dose of prespecified drug(s) to the cumulative planned dose multiplied by a time-correction factor. Lower DI (intended or relative) was associated with inferior survival in 7 of 9 studies reporting crude survival analyses. Multivariable analysis using DI as a covariate was performed in 10 studies. Six showed an association (P < .05) with adjustment for other covariates, and 4 did not. Most studies and those larger studies of higher quality showed poorer outcomes associated with reduced DI. In subgroups aged ≥80 years, survival was not consistently affected by reduced DI. DI-specific randomized trials are warranted, but these data support full-dose R-CHOP in elderly and fit patients aged <80 years with DLBCL, but not in those aged ≥80 years, where dose-reduced R-CHOP does not appear to compromise survival.

Feasibility of high-dose methotrexate administered on day 1 of (R)CHOP in aggressive non-Hodgkin lymphomas

“…Maintaining (R)CHOP dose intensity is a priority as it is associated with better clinical outcomes. 12 In addition, better control of systemic disease might reduce the risk of CNS involvement. 43,44 In patients with known CNS involvement, maintaining the dose intensity of both HDMTX and (R)CHOP is crucial, as HDMTX is an integral component of the treatment plan.…”

“…This can be a particular concern as R-CHOP dose intensity is an independent predictor of outcomes in DLBCL, whereas the overall risk of CNS relapse is relatively low in comparison. 3,12 Whether used for treating known CNS involvement or as prophylaxis, it is imperative that HDMTX be administered in a manner that minimizes toxicity and preserves treatment dose intensity.…”

Risk of febrile neutropenia in very elderly patients aged ≥80 years receiving their first cycle of R‐CHOP regimen: a nationwide real‐world study in Japan

“…Although reduction in chemotherapeutic dose was reported to be a risk factor for impaired treatment effect, 15,16 the risk may be minimized in very elderly patients 14 . A systematic review also showed that survival was not affected by reduced dose intensity of R‐CHOP in patients aged ≥80 years 17 . Because dose reduction in very elderly patients has already been attempted in real‐world clinical settings, the present study may not suggest a new practice.…”

“…14 A systematic review also showed that survival was not affected by reduced dose intensity of R-CHOP in patients aged ≥80 years. 17 Because dose reduction in very elderly patients has already been attempted in real-world clinical settings, the present study may not suggest a new practice. However, the findings may have importance in providing new evidence for current practice.…”

Poor Prognosis of Diffuse Large B-Cell Lymphoma of the Breast: The Role of Dose-Dense Chemotherapy

“…The addition of rituximab to CHOP remains controversial and some studies have reported improved outcomes while most did not observe any benefit. [13][14][15]…”