Abstract
Background and Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Currently, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP) and the prognostic stratification is performed by the Revised International Prognostic Index (R-IPI), identifying 3 distinct prognostic groups with a very good, good and poor outcome. A lot of new prognostic markers have been introduced into the clinical practice to perform better pts' stratification. Particular prognostic relevance has been attributed to serum albumin (SA), β2-microglobulin (B2M), peripheral blood lymphocyte/ monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR) etc. However the data of these prognostic factors across the different R-IPI prognostic groups are limited. Therefore, we decided to access whether SA, B2M, LMR and NLR were predictors of overallsurvival (OS) across the different R-IPI groups of R-CHOP treated DLBCL pts.
Patients and Methods: We retrospectively reviewed the clinical outcome of 281 R-CHOP treated DLBCL pts with median age 58 years and 51.8 % male. According to the R-IPI score, the pts in very good, good and poor risk were 24.2%, 54.8% and 21%, respectively. Laboratory levels of albumin, absolute lymphocyte, monocyte and neutrophil count were recorded, and LMR and NLR - calculated. Serum B2M levels were measured by radioimmunoassay. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models.
Results: The estimated 5-year OS was 87.1%, 74% and 31% for R-IPI very good, good and poor-risk patients, respectively. The median values of SA, B2M, LMR and NLR were 40.7 g/L, 2.9 mg/L, 2.95 and 2.86, respectively. Our data showed that on univariate analysis inferior OS was associated with decreased SA (≤39.4 g/L; 95% confidence interval (CI) 0.70-0.82, p=<0.001), elevated B2M (>2.6 mg/L; 95% CI 0.68-0.80, p=<0.001), reduced LMR (≤2.16; 95% CI 0.71-0.81, p=<0.001) and increased NLR (>2.61; 95% CI 0.66-0.77, p=<0.001), presented as dichotomized variables. On multivariate analysis the independent prognostic significance was confirmed only for SA and LMR, with hazard ratios of 0.23 (95% CI 0.11-0.49, p<0.001) and 0.41 (95% CI 0.21-0.81, p=0.011), respectively.
Based on the dichotomized SA and LMR values a SA/LMR prognostic index (PI) was created stratifying patients into 3 risk groups: very good (SA >39.4 g/L and LMR >2.16; n=75), good (SA ≤39.4 g/L or LMR ≤2.16; n=52) and poor-risk (SA ≤39.4 g/L and LMR ≤2.16; n=41) populations. The estimated 5-year OS was 88.7% for very good, 51.7% for good, and 8.8% for poor SA/LMR PI group (p<0.001). Median OS for poor-risk patients was 1.1 years (95% CI 1.03-1.72 years) and not reached for both the very good and good-risk groups.
We sought to determine whether the SA/LMR PI may provide additional prognostic information within the R-IPI risk groups. Due to low number of deaths - 4.4% (3/68), no statistics could be calculated in very good R-IPI risk group. Within the R-IPI good risk patients SA/LMR PI allowed us to discriminate 3 subgroups, characterized by significant differences in 3-year and median OS (Figure 1): a SA/LMR PI poor risk subgroup (n=18) with 10.4% 3-years OS and 1.13 years (95% CI 0.82-1.44 years) median OS; a SA/LMR PI good risk subgroup (n=32) with 59.5% 3-years OS and median not reached; and a SA/LMR PI very good risk subgroup (n=50) with not reached median OS and 91.3% 3-years OS comparable to the OS in R-IPI very good patients (p=0.229). Only SA retained its independent prognostic significance in R-IPI poor risk group.
Conclusion: SA and LMR are independent prognostic markers to predict survival in DLBCL pts. Adding these variables to prognostic models such as the R-IPI score might improve their predictive ability, providing particularly relevant information within the R-IPI good risk group. A subgroup of R-IPI good risk pts with a very good SA/LMR PI was identified, comparable to the R-IPI very good risk category in terms of OS.
Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis
Overall survival of R-CHOP treated R-IPI good risk DLBCL patients according to SA and LMR at diagnosis
No relevant conflicts of interest to declare.
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal