Conflicting results have been reported about the association between obesity and survival in diffuse large B-cell lymphoma (DLBCL). Some studies have shown improved survival with increased body mass index (BMI), whereas other studies have not supported this association, making the relationship between body weight and survival in DLBCL unclear. Moreover, many of the earlier studies were based on smaller datasets (sample sizes) and/or patient populations who were not treated with rituximab, making the interpretation of these results less clear in the current Rituximab era. Thus, the aim of this study was to investigate the relationship between BMI and survival in non-Hodgkin lymphoma (NHL) patients treated with rituximab containing chemotherapy in a large population-based database in Ontario, Canada.
We conducted a population-based retrospective cohort study using an administrative database in the Ontario Cancer Registry (OCR) in Ontario, Canada. Incident cases of aggressive histology lymphoma treated with a rituximab containing chemotherapy regimen for curative intent were captured between January 1st, 2008 and October 31st, 2016 using the database from the New Drug Funding Program in Cancer Care Ontario, which provides universal public funding of rituximab for this indication. Exclusion criteria included patients who were < 18 years of age, had diagnosis of HIV, or received rituximab > 6 months from time of diagnosis. Aggressive histology lymphoma was defined according to morphology codes in the OCR, and included DLBCL and Burkitt lymphoma. BMI at time of diagnosis was calculated by dividing weight in kilogram (Kg) by height in meter (m2). We first categorized subjects according to low BMI (≤25 Kg/m2) and high BMI (>25 Kg/m2), and then by the World Health Organization (WHO) criteria for BMI as underweight (<18.5 Kg/m2), normal weight (18.5-24.9 Kg/m2), overweight (25-29.9 Kg/m2) and obese (≥ 30 Kg/m2) for subsequent analyses. Subjects were followed from time of first treatment until death (all-cause). Cox proportional hazard models were used to estimate the impact of BMI on overall survival, after adjusting for explanatory variables, such as age, sex, rural/urban residence, income quintile, and comorbidities (Charlson Comorbidity Index). Survival was estimated using Kaplan-Meier analysis, and statistical comparisons were made using the log-rank statistic.
A total of 7046 patients with aggressive histology NHL treated with a rituximab containing chemotherapy regimen were identified. After excluding 1,075 patients due to implausible or missing BMI data, 5,971 patients were included in the study cohort (Table 1).
Kaplan-Meier analysis demonstrated decreased mortality in the overweight and obese groups, and increased mortality in the underweight group, as compared to normal weight group (Figure 1). Multi-variable analyses revealed that increased BMI had a protective effect on overall survival; the rate of all-cause mortality was lower in the high BMI group (HR 0.82; 95% CI 0.74-0.90) compared to the low BMI group. Furthermore, when BMI was categorized by WHO criteria the rate of all-cause mortality was lower in overweight (HR 0.87; 95% CI 0.78-0.97) and obese (HR 0.77; 95% CI 0.68-0.86) groups compared to the normal weight group (Table 2).
When BMI was analyzed as a continuous variable, multivariable analyses revealed that an incremental increase in per unit of BMI was associated with an increased rate of overall survival with a HR of 0.98; 95% CI 0.97-0.99.
In the largest cohort to-date and with all patients treated with rituximab containing chemotherapy, we show that increased BMI in patients with aggressive histology NHL is associated with improved survival. Hypotheses for improved survival at higher BMIs include higher cumulative anthracycline doses due to its lipophilic nature, and the ability of overweight and obese patients to tolerate more intense chemotherapy regimens with less dose reductions that is known to improve survival. These results have important implications for NHL patients in North America where two-thirds of the population is overweight or obese, and more research is needed to explore the possible mechanisms of improved survival with increased body weight in NHL.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.