Proposal of New Prognostic Index for Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

Abstract

BackgroundThe International Prognostic Index (IPI) has been useful prognostic tool to predict prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Since the advent of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for diffuse large B-cell lymphoma (DLBCL), its utility has been challenged and other prognostic index including revised IPI and National Comprehensive Cancer Network (NCCN)-IPI were proposed, which are not popularly used yet. We aimed to develop new prognostic model for DLBCL in rituximab era.MethodBetween March 2004 and June 2012, patients with DLBCL treated with R-CHOP were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. Primary end point was to devise a new prognostic index for DLBCL. Secondary end point was to validate the NCCN-IPI in our cohort. We tested new prognostic index model in the training set of AMC cohort consisted of randomly selected 80% of the sample (503 patients). The remaining 20% (118 patients) was used as an internal validations set.ResultsThe AMC cohort consisted of 621 patients. Median follow-up duration was 43.3 months (6.2-122.5 months). Baseline characteristics of AMC cohort are presented in table 1. Median age was 57 years (range, 16-85 years). Median ϐ-2 microglobulin (ϐ-2 MG) was 2.10 mg/L (range, 1.0-66.0 mg/L). The univariate analysis of baseline characteristics revealed that age (≦60 vs. >60 years), LDH (within normal vs. increased), ECOG performance (0 or 1 vs. ≧2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≦1 vs. >1), B symptoms (no vs. yes), and ϐ-2 MG (≦2.5 vs. >2.5) could predict overall survival (OS), whereas bulky disease and gender did not (p value 0.140, 0.621, respectively). In the multivariate analysis, age, LDH, ECOG performance status, and ϐ-2 MG were significantly associated with OS (p value 0.001, <0.001, 0.004, and 0.019, respectively), while stage, extra-nodal involvement, and B symptom did not (p value 0.057, 0.233, and 0.577, respectively). We developed a new prognostic model with these 4 significant factors in the multivariate analysis. One point is assigned for each of the risk factors without refined categorization. Four risk groups were composed as followings: low (0 point), low-intermediate (1 point), high-intermediate (2-3 points), and high (4 points). The new prognostic model showed better discriminative power compared with classic IPI (Figure 1A). Five-year OS of low- and high-risk subgroup in new scoring model and classic IPI model in AMC cohort were 95% and 32% versus 89% and 45%, respectively. Our model was validated in an internal validation set (Figure 1B). NCCN-IPI also could stratify four risk groups (Figure 1 A and B).ConclusionWe propose a new prognostic index model for DLBCL in rituximab era with age, LDH, ECOG performance and ϐ-2 MG, which has good discriminative power and convenient to apply. It warrants further validation using an independent cohort.Table 1Baseline CharacteristicsCharacteristicsTotalN=621 %Training setN=503 %Validation setN=118 %Age, yearsMedian, range≦ 60 years> 60 years57.0 377 24416-85 60.7 39.357.0 300 20316-84 59.6 40.457.0 77 4117-85 65.3 34.7SexMaleFemale343 27855.2 44.8273 23054.3 45.770 4859.3 40.7ECOG PS0 or 1≧ 2569 5291.6 8.4462 4191.8 8.2107 1190.7 9.3Serum lactate dehydrogenase levelsNormalElevated334 28753.8 46.2279 22455.5 44.455 6346.6 53.4Ann Arbor stageI and IIIII and IV293 32847.2 52.8236 26746.9 53.157 6148.3 51.7Number of extranodal sites<2≧ 2403 21864.9 35.1329 17465.4 34.674 4462.7 37.3B symptomsNoYes549 7288.4 11.6447 5688.9 11.1102 1686.4 13.6International prognostic indexLow/low-intermediateHigh-intermediate/high404 21765.1 34.9327 17665.0 35.077 4165.3 34.7¥Â -2 microglobulin, mg/LMedian, range≦ 2.5 mg/L> 2.5 mg/L2.1 422 1991.0-66.0 68.0 32.02.1 339 1641.0-29.6 67.4 32.62.1 83 351.0-66.0 70.3 28.7Table 2Multivariate Analysis for Factors Associated with Overall SurvivalFactorsHR95% CIP valueScoreAge, years≦ 60 years> 60 years1.000 2.0511.362-3.0900.0011Serum lactate dehydrogenase levelsNormalElevated1.000 3.1651.951-5.135<0.0011ECOG PS0 or 1≧ 21.000 2.0731.261-3.4070.0041ϐ -2 microglobulin, mg/L≦ 2.5 mg/L> 2.5 mg/L1.000 1.6911.0391-2.6220.0191 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.