Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

Abstract

Background The increasing incidence of diffuse large B‐cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co‐morbidity, frailty, and reduced organ and physiological reserve contribute to treatment‐related complications. The optimal dose intensity of R‐CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. Objectives and Methods We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009–2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. Results Porgression‐free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70–79 years (P < 0.001). In contrast, 2‐year cumulative relapse incidence, when accounting for non‐relapse mortality as a competing risk, was no different between 70–79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS‐G: 0–6 vs. >6) (P = 0.27). In 70–79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70–79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). Conclusion ‘R‐mini‐CHOP' provides adequate lymphoma‐specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.

Outcome and determinants of failure to complete primary R‐CHOP treatment for reasons other than non‐response among patients with diffuse large B‐cell lymphoma

“…In a Danish population‐based study, 18.6% of patients received 3‐5 cycles, although also including patients with stage I disease managed with 3 cycles + RT. Similarly, in 690 consecutive British patients aged ≥70 treated with R‐CHOP, only 71% of patients completed at least six cycles of R‐CHOP 22 . In a Portuguese multicenter study including 378 patients aged 60 or above, 23% did not complete planned treatment 23 .…”

Male gender is an independent predictor for worse survival and relapse in a large, consecutive cohort of elderly DLBCL patients treated with R‐CHOP

“…total CIRS‐G score divided by number of co‐morbidities)*, IDI*, ratio of IDI to relative dose intensity* (*analysed as continuous variables). Across all ages, on multivariable analysis when accounting for potential cofounders as listed in Eyre et al (), male gender was independently associated with an inferior PFS [HR 1·64 (95% CI 1·25–2·15); P < 0·001], OS [HR 1·56 (95% CI 1·18–2·05); P = 0·002] and cumulative relapse before death [HR 1·49 (95% CI 1·04–2·25); P = 0·03] (Table SII).…”

“…We recently described the relationship between intended dose intensity (IDI), age and outcome in 690 consecutive patients ≥70 years with DLBCL treated across 8 UK centres (2009–2018) (Eyre et al , ). Herein we investigate the effect of gender on outcome in more detail.…”

“…Median follow‐up was 2·8 years (range 0·4–8·9). 2‐year PFS and OS was 67% (95% CI 63–70%) and 69% (95% CI 65–73%), respectively (Eyre et al , ).…”

The Prognostic Impact of Comorbidities in Patients with De-Novo Diffuse Large B-Cell Lymphoma Treated with R-CHOP Immunochemotherapy in Curative Intent

“…The inferior outcome in patients with high comorbidity might be explained in part by a trend towards prolonged treatment duration, a reduced dose intensity as well as an increase in therapeutic interruptions. These findings suggest that integration of comorbidities might be helpful as a means of identifying patients at high risk for treatment toxicity as well as vulnerable patients, in whom attenuated therapy may be a more reasonable treatment option [4,39,40]. The finding that relapse-free survival was not associated with the burden of comorbidity, whereas it was an independent prognostic factor for OS, might reflect that patients with high comorbidities are at increased risk for other causes of death.…”