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Reduced-dose R-CHOP effective for certain elderly patients with DLBCL
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A reduced-dose regimen of rituximab and CHOP chemotherapy, referred to as R-mini-CHOP, sufficiently controlled lymphoma-specific disease among elderly patients with diffuse large B-cell lymphoma, according to results of a retrospective study published in Journal of Internal Medicine.
The regimen — which includes rituximab (Rituxan; Genentech, Biogen) and 25 mg/m2 doxorubicin, 400 mg/m2 cyclophosphamide and 1 mg vincristine — appeared to be a reasonable treatment option for patients aged 80 years or older seeking a cure, according to researchers.
Although previous studies confirmed the efficacy of R-mini-CHOP among elderly patients, the current study specifically explored the influence of intended dose intensity and relative dose intensity of the combined average dose of cyclophosphamide and doxorubicin, age and comorbidities on outcomes of elderly patients with DLBCL.
“There remains an open question as to what dose intensity of R-CHOP is necessary in different ages with variable frailty and comorbidity burden in order to optimize outcome,” Toby Eyre, MD, hematologist in the department of hematology at Churchill Hospital of Oxford University Hospitals, and colleagues wrote. “To date, no randomized trials comparing cyclophosphamide and doxorubicin dose(s) in elderly [patients with DLBCL] have been performed.”
Eyre and colleagues analyzed toxicity and survival outcomes among 690 patients (median age, 77.1 years; 51% men) from eight U.K. centers receiving R-CHOP with curative intent for untreated de novo DLBCL or untreated transformed indolent B-cell non-Hodgkin lymphoma.
Among patients aged 70 to 79 years (n = 452), most had a combined doxorubicin and cyclophosphamide intended dose intensity close to 100%, whereas patients aged 80 and older (n = 238) typically had an intended dose intensity of 50%.
After median follow-up of 2.8 years (range, 0.4-8.9), 71% of the patients (n = 493) had completed six cycles of R-CHOP.
Results showed median PFS among all patients of 5.1 years (95% CI, 4.1-6.4) and median OS of 4.8 years (95% CI, 4.2-6.4). Researchers noted that median PFS was longer than median OS because they censored eight patients for PFS whose relapse status was unconfirmed at time of death.
Incidence of relapse before death was 19% (95% CI, 16-22) at 1 year and 22% (95% CI, 19-26) at 2 years.
Compared with patients aged 70 to 79 years, significantly fewer patients aged 80 years and older achieved 2-year PFS (60% vs. 71%; P < .001) and OS (59% vs. 74%; P < .001).
Two-year cumulative relapse incidence, when considering nonrelapse mortality as a competing risk, did not differ between the two age groups (univariable subhazard ratio = 1.2; 95% CI, 0.87-1.67).
Whereas patients aged 70 to 79 years demonstrated significantly improved PFS and OS and a lower cumulative relapse rate with an intended dose intensity of 80% or more vs. an intended dose intensity of less than 80% (P < .001), no such differences occurred among patients aged 80 years and older. This suggests that the inferior survival rates among these older patients are driven primarily by nonrelapse mortality, Eyre and colleagues wrote.
The study’s retrospective and nonrandomized nature and the lack of data on patients with DLBCL who were ineligible for anthracycline-based curative treatment served as limitations to this study.
“We show no clear benefit in reducing relapse risk by increasing intended dose intensity to [80% or higher] in patients [aged 80 years and older] compared to other patients of the same age receiving intended dose intensity [less than] 80%,” Eyre and colleagues wrote. “Together this suggests ‘R-mini-CHOP’ dosing provides adequate lymphoma-specific disease control and represents a reasonable treatment option in elderly patients [aged 80 years and older] aiming for a curative approach.” – by John DeRosier
Disclosures: The authors report no relevant financial disclosures.
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