Cell of Origin (COO) Association with High Body Mass Index (BMI) and Overall Survival (OS) in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Maignan Kathleen , Azzam Shaked Peleg , Adamson Blythe , Parrinello Christina M. , Carson Kenneth R. 
Published: November 2019

Introduction:
Overweight and obesity are associated with an increased incidence of DLBCL as well as reduced mortality in DLBCL patients (Carson, et al 2012). Patients with germinal center B-cell-like (GCB) DLBCL have improved overall survival compared to those with non-GCB. We aimed to gain insight into the effect of COO on the relationship between high BMI and overall survival benefit in DLBCL.
Methods:
The sample for this analysis included patients diagnosed with DLBCL between 1/1/2011 and 5/31/2019, using the nationwide Flatiron Health electronic health record (EHR)-derived database, comprised of de-identified patient-level structured and unstructured data, curated via technology-enabled abstraction. Baseline BMI levels were derived from mean height across follow-up and maximum weight closest to, but within 1 year prior to and 30 days after diagnosis date, and were defined as high (obese [≥30] or overweight [25 to <30]), normal (18.5 to <25), and underweight (<18.5). Immunohistochemical (IHC) testing was abstracted from pathology reports or clinical notes. COO was obtained by chart abstraction or determined using the Hans algorithm. Patients were excluded from this analysis if they had underweight BMI, missing BMI, missing COO, or date of diagnosis was >90 days before their start of activity in the database, as this may be an indication of missing data. The association of baseline high BMI with GCB COO was assessed using multivariable logistic regression. The role of COO in the association of BMI and OS was evaluated using multivariable Cox proportional hazards modeling by testing the interaction between BMI and COO, as well as stratifying by COO. Institutional Review Board approval with waiver of informed consent was obtained prior to study conduct.
Results:
The study included 3,010 pts with DLBCL. Obese and overweight patients (n=2,081) had a higher frequency of GCB COO than those with normal weight (n=929) (60.6% vs. 56.6%), with an odds ratio of 0.85 (95% CI: 0.73, 0.99) when adjusting for age and transformation. Survival analyses suggested a lower risk of mortality for overweight and obese patients compared to normal weight patients (hazard ratio [HR]=0.88; 95% CI: 0.76,1.01) when adjusting for age, stage at diagnosis, presence of B-symptoms, COO, and practice type. The tested interaction between BMI and COO was not significant (p=0.26). Stratification by COO found the relationship between BMI and OS among GCB patients (n=1,787) had an adjusted HR of 0.82 (95% CI: 0.68,0.99) and among non-GCB (n=1,223) an adjusted HR of 0.96 (95% CI: 0.76,1.20).
Conclusions:
Overweight and obese patients were more likely to have GCB DLBCL than patients with normal weight. High BMI status was also associated with overall survival benefit, though this was not statistically significant. Stratified analyses suggested that BMI is related to OS in GCB patients but not related in non-GCB. There was insufficient evidence to conclude that the association of BMI and mortality was significantly different by COO status. These findings should be confirmed in other patient cohorts using more specific COO testing modalities and accounting for co-morbidities, but remain thought provoking. There is a known risk of misclassification of COO when it is determined by IHC, however, it is unlikely that this would systematically bias these observations.

Disclosures
Maignan: Flatiron Health Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding; Roche: Equity Ownership. Azzam:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding; Roche: Equity Ownership. Adamson:Roche: Equity Ownership; Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding. Parrinello:Roche: Equity Ownership; Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding. Carson:Flatiron Health, Inc., which is an independent subsidiary of the Roche Group: Employment, Research Funding; Roche: Equity Ownership.