Obesity Is a Prognostic Factor in Elderly Female Patients with Aggressive B-Cell Lymphomas Treated with R- CHOP
Authors: Hohloch Karin , Altmann Bettina , Pfreundschuh Michael , Loeffler Markus , Schmitz Norbert , Ziepert Marita , Truemper Lorenz H. 
Published: October 2019

Abstract
Background: Obesity occurs in more than 20% of patients (pts) above 65 years. In solid tumors e.g. breast or colorectal cancer, outcome of obese patients is inferior when compared to normal weight patients. In lymphoma patients data so far are controversial, while recently published data showed that obesity in lymphoma patients was not associated with inferior outcome.
Methods: 576 patients with aggressive B-cell lymphomas included in the RICOVER60 study ( 6 or 8 cycles CHOP-14 + 8 doses of Rituximab) were analysed as training set. 151 patients from the RICOVER-noRTh study were used as validation set. We analysed EFS, PFS and OS with regard to body mass index (BMI ≥ 30 vs. < 30) and gender. No significant changes in body weight/BMI occurred during treatment, therefore BMI at cycle 1 was used for analysis. In Cox regression models BMI was adjusted for known prognostic factors.
Results: All pts. were > 60 years of age (36% > 70 years), 46% female., 1% pts. low weight (BMI <18.5), 38% normal weight (18.5≤BMI<25), 42% overweight (25≤BMI<30) and 19% pts. obese (BMI≥30). Clinical characteristics were well balanced between training and validation set and between obese (BMI≥30) and non-obese patients (BMI<30). 71% of patients (73% male pts., 70% female pts.) completed therapy per protocol. Pts. with BMI ≥ 30 received less frequently complete treatment (61%) than patients with BMI < 30 (74%; no gender differences). There was no difference between obese/non-obese patients regarding hematotoxicity or infection during cycles. EFS, PFS and OS according to BMI (BMI ≥ 30 vs. BMI < 30) showed no significant difference for all and for male pts., but in female pts. EFS (p=0.041), PFS (p=0.038) and OS (p= 0.031) was significant better for non-obese pts. (figure 1). In a multivariate analysis adjusting for IPI risk factors (LDH>N, ECOG>1; stage III/IV, extra nodal involvement >1) these results were confirmed with the following hazard ratios (HR) for obesity (BMI≥ 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4; male patients - 1.2/1.2/1.0; female patients - 1.7/1.9/2.0 (table 1). These results were consistent also after additional adjustment for age > 70 years, radiotherapy (yes/no) and relative dose. The findings could be validated in an independent validation set of 151 patients from the RICOVER-noRTh study. The HR for EFS/PFS/OS are: all patients - 1.4/1.4/1.7; male patients - 0.7/0.9/1.5; female patients - 2.6/2.0/1.8. Due to small sample size only the HR for female patients for the EFS is significant (p=0.031).
Conclusion: Obesity is a risk factor in elderly female pts. with aggressive B-cell lymphoma treated with R-CHOP with regard to EFS, PFS and OS, adjusted for IPI factors. Sex and weight independently affects rituximab clearance. Females are reported to have slower rituximab clearance with better outcome in the elderly and the rituximab clearance increases with body weight. Therefore worse outcome for obese female patients might be the result of faster rituximab clearance in obese females.
Table 1: Multivariate analysis adjusting for IPI risk factors: HR for Obesity (BMI ≥ 30)
All pts. male pts. female pts.
EFS HR 1.4 [95%CI 1.0-1.9; p= 0.067] HR 1.2 [95%CI 0.7-2.0; p=0.473] HR 1.7 [95%CI 1.0-2.7; p=0.032]
PSF HR 1.4 [95%CI 1.0-2.0; p= 0.080] HR 1.2 [95%CI 0.7-2.1; p=0.558] HR 1.9 [95%CI 1.1-3.2; p=0.022]
OS HR 1.4 [95%CI 0.9-2.1; p= 0.114] HR 1.0 [95%CI 0.5-2.0; p=0.956] HR 2.0 [95%CI 1.1-3.4; p=0.017]

Disclosures
Hohloch: Spectrum: Research Funding; Spectrum, Roche: Other: Advisory board. Pfreundschuh:Roche: Honoraria; Boehringer Ingelheim, Celegene, Roche, Spectrum: Other: Advisory board; Amgen, Roche, Spectrum: Research Funding. Schmitz:Roche, Takeda, Gillead, Riemser und ctilifesciences: Other: Advisory board, Speakers Bureau. Truemper:Sandoz, Celgene, AMGEN, Nordic Nanovector: Other: Advisory board; Amgen, roche, Mundipharma: Research Funding.