Research suggests higher dose intensity R-CHOP (rituximab, cyclophosphamide, doxorubicin hydro-chloride, vincristine sulfate, and prednisone) can improve survival in patients with diffuse large B-cell lymphoma (DLBCL) who are younger than age 80, while full dose intensity R-CHOP in patients age 80 or older lacks the same robust efficacy. However, despite its association with poorer outcomes, reduced dose intensity R-CHOP does not consistently appear to compromise survival in older patients with DLBCL, according to a study published in Blood Advances.
A team of international researchers led by Edward Bataillard, MD, of the Imperial College Healthcare National Health Service Trust, in London, conducted a systematic review of survival outcomes from 13 studies, each enrolling more than 100 patients with DLBCL.
Of 380 unique articles identified in the literature search, Dr. Bataillard’s team selected 13 retrospective studies for review, including six single-center studies, seven multicenter studies, and three analyses of nationwide cancer registries. Overall, a total of 5,188 patients were included.
A pooled cohort of 4,083 patients across 12 studies received either R-CHOP or an R-CHOP-like regimen. Patients in seven of the 12 studies received 21-day cycles of R-CHOP at either the full dose or reduced dose (R-miniCHOP). A small number of patients in three studies received other regimens, including:
- R-CVP (cyclophosphamide, vincristine, prednisolone, rituximab)
- R-CNOP, CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisolone, with or without rituximab)
- R-CHOEP/EPOCH-R, CHOEP/EPOCH (etoposide with cyclophosphamide, doxorubicin, vincristine, prednisolone, with or without rituximab)
While there was variation across studies in how relative dose intensity (RDI) was defined, all 13 studies assessed RDI. The median RDI, reported in four studies, ranged between 58.9% and 87.9%. A total of seven out of nine studies found a significant reduction in overall survival (OS) with reduced RDI versus patients who received higher RDIs (p<0.05).
In one study, the researchers reported an inverse association between RDI and survival in an elderly U.S. veteran population. This study reported a significantly higher median survival in the reduced RDI cohort versus the higher RDI cohort (28.1 months vs. 21.8 months, respectively; p=0.029).
Another study found patients who received RDI at 85% or higher had a significantly worse OS compared with patients who had reduced doses (p=0.029).
In a different study, there was a trend toward better OS in patients ages 75 to 79 who received higher intended dose intensity (IDI). Another study found IDI of 80% or higher was associated with greater progression-free survival and OS among patients ages 70 to 79 versus 80 and older. Additionally, there was a significantly higher cumulative incidence of relapse in patients between 70 and 79 years old who received an IDI of less than 80% (p=0.04).
Overall, several of the studies in the review found diminishing survival with R-CHOP dose intensity as the age of the patients progressed. The maintenance of a higher RDI held either a weak or no association with improved OS, while one study found a higher RDI was detrimental to survival. “This result may be explained by the fact that among the very elderly, the risk of dying of lymphoma-unrelated causes is much more significant and dilutes the potential deaths caused by suboptimal lymphoma treatment,” the authors wrote.
The researchers noted that prospective studies of dose intensity are needed, given the reported “absence of improved options beyond R-CHOP in DLBCL over the past 20 years.”
Bataillard EJ, Cheah CY, Maurer MJ, Khurana A, Eyre TA, El-Galaly TC. Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: A systematic review. Blood Adv. 2021;5:2426-2437.