A population-based multistate model for diffuse large B-cell lymphoma-specific mortality in older patients

• Type of Material: Article
• Authors: Caglar Caglayan, Georgia Institute of Technology; Jordan S. Goldstein, Emory University; Turgay Ayer, Georgia Institute of Technology; Ashish Rai, American Cancer Society Inc.; Christopher R Flowers, Emory University
• Language: English
• Date: 2019-06-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 American Cancer Society
• Final Published Version (URL): http://dx.doi.org/10.1002/cncr.31981
• Title of Journal or Parent Work: Cancer
• ISSN: 0008-543X
• Volume: 125
• Issue: 11
• Start Page: 1837
• End Page: 1847
• Grant/Funding Information: Research reported in this publication was supported in part by grants from the Burroughs Wellcome Fund Innovation in Regulatory Science Award and the National Cancer Institute (grant K24CA208132) to Christopher R. Flowers.
• Keywords: cyclophosphamide; COMPETING RISKS; SURVEILLANCE; RACIAL-DIFFERENCES; DLBCL-associated mortality; and prednisone (R-CHOP) treatment; Science & Technology; survival analysis; RANDOMIZED CONTROLLED-TRIAL; multistate model; DETUDE-DES-LYMPHOMES; vincristine; COMPREHENSIVE GERIATRIC ASSESSMENT; Life Sciences & Biomedicine; CHEMOTHERAPY PLUS RITUXIMAB; diffuse large B-cell lymphoma (DLBCL); rituximab; R-CHOP; Oncology; SURVIVAL; doxorubicin; ELDERLY-PATIENTS
• Research Categories: Health Sciences, Oncology; Health Sciences, Epidemiology

Abstract

Background: Despite effective therapies, outcomes for diffuse large B-cell lymphoma (DLCBL) remain heterogeneous in older individuals due to comorbid diseases and variations in disease biology. Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors conducted a multistate survival analysis of 11,780 patients with DLBCL who were aged ≥65 years at the time of diagnosis (2002-2009). Cox proportional hazards models were used to specify the impact of prognostic factors on overall survival and cause-specific deaths, and the Aalen-Johansen estimator was used to project the course of DLBCL over time with or without standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Results: Advanced age (hazard ratio [HR] for ages 71-75 years: 1.25; HR for ages 76-80 years: 1.46; HR for ages 81-85 years: 1.88; and HR for age ≥86 years: 2.26), DLBCL stage (HR for Ann Arbor stage II: 1.28; HR for stage III: 1.54; and HR for stage IV: 1.95), Charlson Comorbidity Index (CCI) ≥1 (HR for CCI of 1, 1.15; and HR for CCI >1, 1.37), and not being married (HR, 1.12) were associated with an increased risk of DLBCL-specific death. Being female (HR, 0.91) and of higher socioeconomic status (HR, 0.91) were associated with a lower risk of DLBCL-related mortality after therapy. For patients treated with R-CHOP (3610 patients), the risk of death due to DLBCL was 14.0% and 18.6%, respectively, at 2 and 5 years of treatment and plateaued afterward, confirming a 5-year “cure” point while receiving R-CHOP among older patients. Conclusions: Conducting a survival analysis over a large data set, the current study evaluated competing risks for death within a multistate modeling framework, and identified age, sex, and CCI as risk factors for DLBCL-specific and other causes of death.