Risk of Febrile Neutropenia in Very Elderly Patients Aged ≥80 Years Who Received R-CHOP Regimen: A Nationwide Analysis in Japan
Authors: Matsuda Kensuke , Jo Taisuke , Shimura Arika Nukina , Honda Akira , Masamoto Yosuke , Yasunaga Hideo , Kurokawa Mineo 
Published: November 2021

Abstract
Background: Despite the aging society, few studies have evaluated risk factors for febrile neutropenia (FN) in the very elderly. This may be due to the difficulty of conducting a prospective study in the presence of comorbidities and a limited number of patients. We retrospectively analyzed risk factors for FN in the first cycle of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in the very elderly aged ≥ 80 years using a nationwide inpatient database in Japan.
Study Design and Methods: This study was a retrospective cohort study using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. The database includes discharge abstracts and administrative claims data from &gt;1200 acute-care hospitals and covers around 90% of all tertiary-care emergency hospitals in Japan. We identified patients aged ≥ 80 years old with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first cycle of R-CHOP regimen between July 2007 and March 2017 from the database. The initial dose intensity (IDI, %) was calculated as the average ratio of the actual dose to the 100% dose of cyclophosphamide and doxorubicin. IDI less than 80% was defined as reduced IDI. Multivariable logistic regression analysis fitted with a generalized estimating equation accounting for within-hospital clustering was performed to identify factors associated with the occurrence of FN. P&lt;0.05 was considered statistically significant.
Results: We identified 1,819 patients aged ≥ 80 years old with DLBCL who were newly diagnosed and treated with R-CHOP. The median age was 83 years (interquartile range: 82-85). A total of 73 (4%) patients received antimicrobial prophylaxis, and 270 (15%) received primary prophylaxis with G-CSF. Reduced IDI of R-CHOP regimen was performed in 1,444 (79%) patients, including 697 patients with 60-80% of IDI and 747 patients with 40-60% of IDI. FN occurred in 115 of the 1,819 patients (6.3%) with a median of 10 days (interquartile range: 8-12) after the administration of cyclophosphamide. Antimicrobial prophylaxis, primary prophylaxis with daily G-CSF, and pegfilgrastim were not significantly associated with a lower occurrence of FN in the very elderly patients (odds ratio 0.69 [95% confidence interval 0.30-2.21], 1.39 [0.73-2.64], 1.43 [0.73-2.81], respectively). Reduced IDI was significantly associated with a lower occurrence of FN (40-60%: odds ratio 0.54 [0.32-0.92]). Advanced-stage lymphoma (&gt;stage 2) and placement of central venous catheter was significantly associated with the occurrence of FN (odds ratio 1.59 [1.02-2.49], 3.19 [1.81-5.62], respectively).
Conclusion: The present nationwide study showed that IDI was reduced in most of the very elderly patients with DLBCL in a real-world clinical practice. The proportion of the very elderly patients who developed FN tended to be lower than those in previous studies with younger patients, which may be explained by reduced IDI in the very elderly. Whereas, prevention strategies with G-CSF for FN may be less effective in the very elderly.

Disclosures
Matsuda: Ono Pharmaceutical: Other: Lecture fee; Kyowa Kirin: Other: Lecture fee. Jo: Tsumura: Other: Lecture fee, Research Funding; AstraZeneca: Other: Lecture fee; Sanofi: Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee. Shimura: Eisai: Other: Lecture fee. Honda: Otsuka Pharmaceutical: Other: Lecture fee; Ono Pharmaceutical: Other: Lecture fee; Nippon Shinyaku: Other: Lecture fee; Jansen Pharmaceutical: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Takeda Pharmaceutical: Other: Lecture fee. Masamoto: MSD K.K.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Yasunaga: Pfizer: Consultancy, Other: Lecture fee; Novartis: Consultancy, Other: Lecture fee; Boehringer Ingelheim: Other: Lecture fee; Chugai Pharmaceutical: Other: Lecture fee; Tsumura: Other: Lecture fee. Kurokawa: MSD K.K.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau.