Primary Prophylaxis with Pegfilgrastim in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Nation-Wide, Propensity Score Based Analysis
Authors: Matsuda Kensuke , Jo Taisuke , Miyauchi Masashi , Toyama Kazuhiro , Nakazaki Kumi , Yasunaga Hideo , Kurokawa Mineo 
Published: November 2019

Background: In the daily practice, clinical effectiveness of pegfilgrastim compared to that of daily filgrastim in patients with malignant lymphoma is still unclear. This study aimed to clarify the effectiveness of pegfilgrastim versus daily filgrastim, using a national inpatient database in Japan.
Study Design and Methods: We retrospectively reviewed 18095 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first R-CHOP treatment between July 2007 and March 2017. Patients who received primary G-CSF prophylaxis were divided into pegfilgrastim group and filgrastim group. Outcomes included incidence of febrile neutropenia, all-cause in-hospital death, length of hospital stay, and total costs. To account for measured confounding, patients' characteristics were adjusted using two different propensity score utilizing methods: propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW). Instrumental variable (IV) analysis was also performed to account for unmeasured confounding.
Results: We identified 1299 patients in the pegfilgrastim group and 2203 patients in the filgrastim group. FN occurred in 380 of the 3502 (11%) total patients with a median of 9 days (interquartile range [IQR] 7-10) after the initiation of the chemotherapy. All-cause in-hospital death occurred in 94 (2.7%) of 3502 patients. Median of hospital stay was 17 days (IQR 13-22), and total medical costs during hospitalization were 7300 (IQR 5700-9500) in USD.
By one-to-one PSM, 1294 patients for both the pegfilgrastim and filgrastim groups were selected. Pegfilgrastim was administered 2 days (median, IQR 1-3) after the chemotherapy. Daily filgrastim administration was initiated 5 days (median, IQR 3-6) after the chemotherapy, and continued for 6 days (median, IQR 2-7). Compared with the filgrastim group, the pegfilgrastim group showed significant lower risk of the FN incidence (risk difference 6.1%, 95% confidence interval [CI] 4.1-8.1) and all-cause in-hospital mortality (risk difference 0.9%, 95% CI 0.05-1.8). In similar, stabilized IPTW showed that pegfilgrastim group was significantly associated with the lower risk of FN (risk difference 7.0%, 95% CI 5.1-8.9) and in-hospital mortality (risk difference 1.8%, 95% CI 0.9-2.7). In PSM, the length of hospital stay and total costs during hospitalization were also significantly decreased in the pegfilgrastim group compared to the filgrastim group (percent reduction 34% [95% CI 31-37], percent reduction 12% [95% CI 9-15], respectively). Stabilized IPTW also showed the significant percent reduction of the pegfilgrastim group to the filgrastim group for length of hospital stay and total costs (31% [95% CI 25-35], 19% [95% CI 13-24], respectively).
In the sensitivity analyses, IV methods showed significantly lower FN susceptibility (odds ratio 0.14, 95% CI 0.07-0.26). However, pegfilgrastim was not associated with the reduction in susceptibility of in-hospital mortality (odds ratio 0.93, 95% CI 0.23-3.70). The ratio of the pegfilgrastim group to the filgrastim group for length of hospital stay and total costs were 55% (95% CI 51-60) and 78% (95% CI 73-84), respectively.
Conclusion: Pegfilgrastim contributed to lower susceptibility of FN. Total length of hospital stay and medical costs were also decreased in the pegfilgrastim group.

Disclosures
Jo: Tsumura: Other: Laboratory of joint program, Research Funding. Miyauchi:kyowa Kirin: Research Funding. Toyama:Bristol-Myers Squibb: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Celgene K.K.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau. Kurokawa:Bristol-Myers Squibb: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; Novartis Pharma K.K.: Research Funding; Yakult Honsha Company: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; Celgene K.K.: Consultancy, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire Japan K.K.: Speakers Bureau; Pfizer Japan Inc.: Research Funding; Sumitomo Dainippon Pharma Co.,Ltd.: Research Funding, Speakers Bureau; Shionogi & Co., Ltd: Consultancy, Honoraria; MSD K.K.: Consultancy, Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Consultancy, Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Bioverativ Japan ltd.: Consultancy.