Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, Illinois.
Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer. 2019 Apr 1;125(7):1143-1154. doi: 10.1002/cncr.31914. Epub 2018 Dec 12.
Granulocyte colony-stimulating factors (G-CSFs), which are used for the prevention of complications from chemotherapy-related neutropenia, are linked to the risk of developing second primary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The objective of this study was to examine the correlation between using a specific G-CSF agent and the risk of MDS/AML among older patients with non-Hodgkin lymphoma (NHL).
This was a retrospective cohort study of adults aged >65 years who were diagnosed with first primary NHL between 2001 and 2011. With data from the Surveillance, Epidemiology, and End Results-Medicare-linked database, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the risk of MDS/AML associated with the receipt of G-CSF(filgrastim and pegfilgrastim) in Cox proportional-hazards models, which were stratified according to treatment accounting for confounding by indication.
Among 18,245 patients with NHL patients who had a median follow-up of 3.5 years, 56% received chemotherapy and/or immunotherapy, and G-CSF was most commonly used in those who received rituximab plus multiple chemotherapy regimens (77%). Subsequent MDS/AML diagnoses were identified in 666 patients (3.7%). A modest increased risk of MDS/AML was observed with the receipt of G-CSF (HR, 1.28; 95% CI, 1.01-1.62) and a trend was observed with increasing doses (P < .01). When specific agents were analyzed, an increased risk of MDS/AML was consistently observed with filgrastim (≥10 doses: HR, 1.67; 95% CI, 1.25-2.23), but not with pegfilgrastim (≥10 + doses: HR, 1.11; 95% CI, 0.84-1.45).
A higher of MDS/AML was observed in patients with NHL risk among those who received G-CSF that was specific to the use of filgrastim (≥10 doses), but not pegfilgrastim. Neutropenia prophylaxis is an essential component of highly effective NHL treatment regimens. The differential risk related to the types of G-CSF agents used warrants further study given their increasing use and newly available, US Food and Drug Administration-approved, biosimilar products.
粒细胞集落刺激因子（G-CSFs）用于预防化疗相关中性粒细胞减少症的并发症，与第二原发性骨髓增生异常综合征（MDS）和急性髓系白血病（AML）的发病风险相关。本研究的目的是研究在接受化疗的老年非霍奇金淋巴瘤（NHL）患者中，使用特定 G-CSF 药物与 MDS/AML 发病风险之间的相关性。
这是一项回顾性队列研究，纳入了 2001 年至 2011 年间被诊断为首次原发性 NHL 的年龄＞65 岁的成年人。利用监测、流行病学和最终结果-医疗保险链接数据库的数据，在 Cox 比例风险模型中估计了与接受 G-CSF（粒细胞集落刺激因子，包括非格司亭和培非格司亭）相关的 MDS/AML 发病风险的调整后的危险比（HR）和 95%置信区间（CI），并按治疗方案进行了分层，以考虑混杂因素。
在中位随访 3.5 年的 18245 例 NHL 患者中，56%接受了化疗和/或免疫治疗，最常使用 G-CSF 的是接受利妥昔单抗联合多种化疗方案的患者（77%）。666 例（3.7%）患者随后被诊断为 MDS/AML。接受 G-CSF 治疗的患者 MDS/AML 发病风险略有增加（HR，1.28；95%CI，1.01-1.62），且剂量越高风险越高（P＜0.01）。当分析特定药物时，发现使用非格司亭（≥10 剂）与 MDS/AML 发病风险增加一致，但使用培非格司亭（≥10 剂）则无此相关性（HR，1.11；95%CI，0.84-1.45）。
与接受培非格司亭（≥10 剂）的患者相比，接受特定于非格司亭（≥10 剂）的 G-CSF 治疗的 NHL 患者的 MDS/AML 发病风险更高。中性粒细胞减少症预防是高效 NHL 治疗方案的重要组成部分。鉴于 G-CSF 药物的使用日益增加，且新获得美国食品和药物管理局批准的生物类似产品，因此，需要进一步研究其与 MDS/AML 发病风险之间的差异。
