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Impact of primary prophylaxis by pegfilgrastim in diffuse large B-cell lymphoma treated with R-CHOP

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Abstract

Febrile neutropenia (FN) and chemotherapy-induced neutropenia (CIN) are common conditions that lead to dose reduction or delayed chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL). Primary prophylaxis (PP) with long-acting granulocyte colony-stimulating factor (G-CSF) was introduced in South Korea in 2014. We aimed to investigate the effects of PP on FN-related hospitalization and death in patients with DLBCL receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Korean individuals (n = 11,491) with incident DLBCL and receiving R-CHOP during 2010–2016 were followed for FN-related hospitalization and mortality. The PP exposure group (patients during 2014–2015, n = 3599), patients during 2010–2016 (n = 11,491), and patients receiving PP during 2014–2016 (n = 4421) were compared with the non-exposure group (patients during July 2011–June 2013, n = 3017), patients in 2013 (n = 1596), and patients not receiving PP during 2014–2016 (n = 1289), respectively. Multivariable-adjusted hazard ratios (HRs) were calculated using the Cox model. The PP exposure group had 16% lower FN-related hospitalizations than the non-exposure group (HR = 0.84, P < 0.001). PP exposure had no beneficial effect on 1-year (HR = 0.98, P = 0.782) and 5-year mortality (HR = 0.97, P = 0.474). Patients in 2014 (HR = 0.85, P < 0.001), 2015 (HR = 0.88, P = 0.003), and 2016 (HR = 0.80, P < 0.001) had a decreased risk of FN-related hospitalizations compared with those in 2013. Among patients receiving their first R-CHOP cycle during 2014–2016, the HR for FN-related hospitalization was 0.90 (P = 0.014) in PP users compared with non-users. PP with a long-acting G-CSF lowered the FN-related hospitalization risk but did not benefit survival in patients with DLBCL receiving R-CHOP.

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Data availability

The data underlying the results presented in the study are available from the National Health Insurance Service (https://nhiss.nhis.or.kr/bd/ab/bdaba000eng.do).

Abbreviations

FN :

febrile neutropenia

CIN :

chemotherapy-induced neutropenia

DLBCL :

diffuse large B-cell lymphoma

PP :

primary prophylaxis

G-CSF :

granulocyte colony-stimulating factor

R-CHOP :

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

HR :

hazard ratio

LOS :

length of hospital stay

NHIS :

National Health Insurance Service

STROBE :

Strengthening the Reporting of Observational Studies in Epidemiology

SD :

standard deviation

ER :

emergency room

Q :

quartile

KRW :

Korean Won

CI :

confidence interval

RCT :

randomized clinical trial

NHL :

non-Hodgkin lymphoma

ASCO :

American Society of Clinical Oncology

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1G1A101383912).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, South Korea

    Moonho Kim, Yongchel Ahn, Heui-June Ahn, Suk-Hun Ha & Ho-Suk Oh

  2. Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, South Korea

    Jae-Seok Song, Woong-Sub Park & Sang-Wook Yi

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  1. Moonho Kim
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Contributions

MK and SWY conceived the study concept and design. SWY acquired the data and performed statistical analyses. MK and SWY wrote the first draft. YA, HJA, SHH, HSO, JSS, and WSP searched the literature. MK, SWY, YA, HJA, JSS, and WSP analyzed and interpreted the data. All authors contributed to the critical revision of the manuscript. All authors have read and approved the final submitted version of the manuscript. SWY is the guarantor of this study, and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Sang-Wook Yi.

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The requirement for informed consent was waived because this study used anonymized data from the NHIS, adhering to a stringent confidentiality protocol.

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Kim, M., Ahn, Y., Ahn, HJ. et al. Impact of primary prophylaxis by pegfilgrastim in diffuse large B-cell lymphoma treated with R-CHOP. Ann Hematol 102, 3167–3175 (2023). https://doi.org/10.1007/s00277-023-05411-2

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