A New Prognostic Model for Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP
Authors: Miura Katsuhiro , Konishi Jun , Miyake Takaaki , Masanori Makita , Hojo Atsuko , Masaki Yasufumi , Uno Masatoshi , Ozaki Jun , Yoshida Chikamasa , Niiya Daigo , Kitazume Koichi , Maeda Yoshinobu , Takizawa Jun , Sakai Rika , Nawa Yuichiro , Yano Tomofumi , Yamamoto Kazuhiko , Sunami Kazutaka , Hiramatsu Yasushi , Aoyama Kazutoshi , Tsujimura Hideki , Hatta Yoshihiro , Kanno Masatoshi 
Published: October 2019

Abstract
Background
Elderly patients with diffuse large B-cell lymphoma (DLBCL) are more likely to face severe adverse events and/or insufficient dose intensity when treated with R-CHOP. The International Prognostic Index (IPI) predicts treatment outcome of patients with DLBCL, but risk stratification for such patients remains uncertain. Thus, we developed a new decision making model, which serves as a guide to the optimal personalized therapy for elderly DLBCL.
Patients and methods
This is a multicenter, retrospective study conducted by Society of Lymphoma Treatment in Japan (SoLT-J). Clinical features and treatment records of patients aged ≥ 65-years old, who had been diagnosed with de novo DLBCL and given at least one cycle of R-CHOP between 2001and 2012, were collected and analyzed for their prognostic significance after receiving approval from each institutional review board. Charlson Comorbidity Index (CCI) (Charlson et al, 1987) was used to access the co-existing medical status. Relative dose intensity (RDI) (i.e. the percentage of actual dose administered per protocol specified dose) for the average of cyclophosphamide and doxorubicin, adjusted by the effect of radiation therapy, was calculated for all patients.
Results
A total of 633 patients with a median 75-years old (range 65-96) treated with a median 6 cycles of R-CHOP (range 1-8) was analyzed. Ninety-six (15%) patients received planned or additional radiation therapy. R-CHOP therapy was discontinued in 129 (20%) patients because of treatment related toxicities, of which 30 (5%) patients died. The advanced age, hypoalbuminemia, and high score of CCI were identified as independent prognostic factors by the backward stepwise analysis for survival. The multivariate Cox regression analysis revealed that age > 75-years, serum albumin concentration < 3.7 g/dl, and CCI score ≥ 3 were significantly associated with worse overall survival (OS), progression free survival (PFS), and treatment related mortality (TRM), independently of IPI score ≥ 3 (Table 1). Regarding the index consisting of these three new risk factors, 135, 270, 184 and 44 patients were scored 0, 1, 2, and 3 point(s), respectively. The elevation of this score was significantly associated with lower average RDI (72% vs 63% vs 48% vs 41%, P < .0001) and more frequent unanticipated discontinuance of the treatment (10% vs 16% vs 31% vs 34%, P < .0001). Accompanied by IPI score ≥ 3, this index discriminated five risk groups with 3-year OS of 88%, 79%, 59%, 38%, and 6% (P < .0001), respectively (Figure 1).
Conclusion
The combination of age, serum albumin concentration, and comorbidities predicts adherence to R-CHOP-and outcome, as well as the IPI-in elderly patients with DLBCL. This prognostic model may help physicians to decide the intensity of the treatment, and needs to be validated further.
Table 1. Multivariate analysis for overall survival, progression free survival, and treatment related mortality. OS PFS TRM Prognostic Factor HR P HR P HR P Age > 75-years 2.16 <.0001* 1.99 <.0001* 2.20 0.0415* Alb < 3.7 g/dl 2.28 <.0001* 1.88 <.0001* 3.90 0.0015* CCI score ≥ 3 2.26 <.0001* 1.89 <.0001* 2.67 0.0185* IPI score ≥ 3 1.72 <.0001* 1.87 <.0001* 1.71 0.1642

Disclosures
Miura: CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; Meiji Seika Pharma: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene K.K.: Honoraria; Astellas Pharma Inc.: Honoraria; Sumitomo Dainippon Pharma Co., Ltd.: Honoraria. Miyake:CHUGAI PHAMACEUTICAL CO., LTD: Honoraria. Masaki:Celgene K.K: Honoraria; TAIHO Phamaceutical Co., Ltd: Research Funding; Asahi Kasei Pharma Corporation: Research Funding; ONO PHAMACEUTICAL CO., LTD: Research Funding; SHIONOGI & CO., LTD: Research Funding; Sumitomo Dainippon pharma Co., Ltd: Research Funding; TEIJIN PHARMA LIMITED: Research Funding; Kyowa Hakko Kirin Company, Limited: Honoraria, Research Funding; Takeda pharmaceutical Compani Limited: Honoraria, Research Funding; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria, Research Funding; Astellas pharma Inc: Research Funding; Eisai Co., Ltd: Honoraria, Research Funding. Sakai:Kyowa Hakko Kirin Company, Limited: Research Funding; Bayer Yakuhin,Ltd: Honoraria; Bristol-Myers Company: Honoraria; FUJIFILM RI Pharma Co., Ltd: Honoraria; Eisai Co., Ltd: Honoraria, Research Funding; SHIONOGI & CO., LTD: Honoraria; Sumitomo Dainippon pharma Co., Ltd: Honoraria; YakuLt Honsya Co., Ltd: Honoraria, Research Funding; Takeda pharmaceutical Compani Limited: Honoraria, Research Funding; Celgene K.K: Honoraria; TAIHO Phamaceutical Co., Ltd: Honoraria, Research Funding; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria, Research Funding. Sunami:Takeda pharmaceutical Compani Limited: Research Funding; ONO PHAMACEUTICAL CO., LTD: Research Funding. Aoyama:Mochida Pharmaceutical Co., Ltd: Honoraria; Kyowa Hakko Kirin Company, Limited: Honoraria; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria. Hatta:CHUGAI PHARMACEUTICAL CO. LTD: Honoraria; Kyowa Hakko Kirin CO., Ltd, Japan: Honoraria; Celgene K.K.: Honoraria. Kanno:Nippon Kayaku Co., Ltd: Research Funding; TAIHO Phamaceutical Co., Ltd: Research Funding; Merck Serono Japan: Honoraria; FUJIFILM RI Pharma Co., Ltd: Honoraria; Mochida Pharmaceutical Co., Ltd: Honoraria; Kyowa Hakko Kirin Company, Limited: Honoraria; CHUGAI PHAMACEUTICAL CO., LTD: Honoraria.