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The influence of comorbidities in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has been modestly investigated. Different comorbidity scoring systems are available for cancer patients.

In order to evaluate the impact of comorbidities on the overall survival (OS) we have performed retrospective analyses of clinical records of the patients with DLBCL treated with R-CHOP, R-EPOCH and R-CVP protocol. The following comorbidity scores were used: Cumulative Illness Rating Scale (CIRS), Charlson Comorbidity Index (CCI), age adjusted CCI (aaCCI) and Hematopoietic-Cell-Transplantation Comorbidity Index (HCT-CI)

A total of 378 patients (195 female/183male) were included in the study. Median age was 58 years (range 18-80). Elderly population (70 years and older) represented 20.2% of analyzed group. According to the Ann Arbor classification, stage I, II, III and IV had 51patients (13.5%), 129 (34.1%), 72 (19%) and 129 (33.3%), respectively. Bulky disease was present in 88 patients (23.3%) and B symptoms in 248 patients (65.6%). Regarding Eastern Cooperative Group (ECOG) performance status (PS), 23.7% of patients had ECOG PS ≥ 2. The most frequent extranodal localization were bone marrow (27.2% of patients) and gastrointestinal tract (28.8% of patients). Revised International Prognostic Index (R-IPI) was represented as low score in 70 patients (18.5%), intermediate in 203 (53.7%) and high in 105 (27.8%). Approximately 55% of patients didn`t have any comorbidity. Regarding comorbidity indexes (CI), CIRS ≥ 17 had 4% of patients (minimal score was 14), CCI ≥ 3 had 3.2%, aaCCI ≥ 5 had 34.1%, and HCT-CI ≥ 2 had 31.2% of patients. The patients were treated with R-EPOCH protocol (13 patients, 34.4%), R-CVP (22 patients, 5.8%), and R-CHOP (343 patients, 90.7%).

Complete and partial remission were achieved in 334 (88.4%) of patients and 44 patients (12.6%) had primary resistant disease. The prognostic value of R-IPI was highly statistically significant (Log Rank χ² 53.569, p < 0.01). The patients with ECOG PS ≥ 2 had poorer outcome than the patients in good PS (Log Rank χ² 33.075, p < 0.01). In patients with CIRS ≥ 17 median OS was 30 months (95% CI 10.147-49.859) comparing to the patients with CIRS 14-16 whose median OS was not reached (Log Rank χ² 10.046, p < 0.01). The patients with CCI ≥ 3 had poorer outcome (median OS of 24 months, 95% CI 0.00-50.877) than the patients with CCI 0-2 (Log Rank χ² 12.659, p < 0.01). The patients with HCT-CI≥2 had significantly poorer outcome than the patients with low CI (Log Rank χ² 8.041, p < 0.01). OS in patients with HCT-CI≥2 after 1, 2 and 5 years was 69%, 63% and 49% respectively, and 89%, 81% and 72% for those with HCT-CI 0-1. The patients treated with R-CHOP and R-EPOCH protocol had statistically significant better OS than the patients treated with R-CVP protocol (Log Rank χ² 8.754, p < 0.01). Multivariant analysis (CIRS, CCI, aaCCI, HCT-CI, therapeutic approach, R-IPI) revealed that the most predictable factor for OS was R-IPI (p < 0.0001).

Comorbidities are an independent prognostic parameters for worse OS in patients with DLBCL treated with immunochemotherapy. Omission of the antracyclines due to the frailty, older age or high comorbidity score leads to significantly poorer outcome. Finally, in the rituximab era prognosis is appreciably influenced with the value of initial R-IPI.