Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri.
Biol Blood Marrow Transplant. 2017 Dec;23(12):2065-2069. doi: 10.1016/j.bbmt.2017.07.023. Epub 2017 Aug 7.
Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization. In retrospective studies, stem cell mobilization with tbo-filgrastim has shown similar efficacy and toxicity as filgrastim, but no prospective studies have been published to date. We have conducted the first prospective randomized trial comparing the safety and efficacy of tbo-filgrastim in combination with plerixafor with that of filgrastim in combination with plerixafor for stem cell mobilization in patients with MM and NHL. This is a phase 2 prospective randomized (1:1) open-label single-institution noninferiority study of tbo-filgrastim and filgrastim with plerixafor in patients with MM or NHL undergoing auto-HSCT. Here 10 µg/kg/day of tbo-filgrastim/filgrastim was administered s.c. for 5 days (days 1 to 5). On day 4 at approximately 1800 hours, 0.24 mg/kg of plerixafor was administered s.c. Apheresis was performed on day 5 with a target cumulative collection goal of at least 5.0 × 10 CD34 cells/kg. The primary objective was to compare day 5 CD34 cells/kg collected. Secondary objectives included other mobilization endpoints, safety, engraftment outcomes, and hospital readmission rate. A total of 97 evaluable patients were enrolled (tbo-filgrastim, n = 46; filgrastim, n = 51). Tbo-filgrastim was not inferior to filgrastim in terms of day 5 CD34 cell collection (mean, 11.6 ± 6.7 CD34 cells/kg versus 10.0 ± 6.8 CD34 cells/kg. Multivariate analysis revealed a trend toward increased mobilization in the tbo-filgrastim arm, but this was not statistically significant. The tbo-filgrastim and filgrastim arms were similar in all secondary endpoints. Tbo-filgrastim is not inferior in efficacy and has similar safety compared to reference filgrastim when used for stem cell mobilization in patients with MM and NHL. Granix can be safely used instead of Neupogen for stem cell collection in patients undergoing auto-HSCT for MM or NHL. The study is registered at https://clinicaltrials.gov/ct2/show/NCT02098109.
自体造血干细胞移植（auto-HSCT）可改善多发性骨髓瘤（MM）和非霍奇金淋巴瘤（NHL）患者的生存率。传统上，粒细胞集落刺激因子（Neupogen；重组 G-CSF）曾被单独使用或与plerixafor 联合用于 auto-HSCT 的干细胞动员。在欧洲，一种生物类似的重组 G-CSF（Tevagrastim）已被批准用于与参照粒细胞集落刺激因子类似的各种适应症，包括用于 auto-HSCT 的干细胞动员；然而，在美国，tbo-粒细胞集落刺激因子（Granix）是根据原始生物制品申请注册的，并未批准用于干细胞动员。在回顾性研究中，tbo-粒细胞集落刺激因子联合 plerixafor 的干细胞动员显示出与粒细胞集落刺激因子相似的疗效和毒性，但迄今为止尚未发表前瞻性研究。我们进行了第一项前瞻性随机试验，比较了 tbo-粒细胞集落刺激因子联合 plerixafor 与粒细胞集落刺激因子联合 plerixafor 用于 MM 和 NHL 患者干细胞动员的安全性和疗效。这是一项在 MM 或 NHL 患者中进行的前瞻性随机（1:1）开放性单中心非劣效性研究，比较 tbo-粒细胞集落刺激因子与粒细胞集落刺激因子联合 plerixafor。在此试验中，皮下给予患者 10 µg/kg/天的 tbo-粒细胞集落刺激因子/粒细胞集落刺激因子，连续 5 天（第 1 天至第 5 天）。第 4 天约 1800 小时，皮下给予 0.24 mg/kg 的 plerixafor。第 5 天进行采集，目标累积采集量至少为 5.0×10 CD34 细胞/kg。主要目标是比较第 5 天 CD34 细胞/kg 的采集量。次要目标包括其他动员终点、安全性、植入结果和住院再入院率。共纳入 97 例可评估患者（tbo-粒细胞集落刺激因子，n = 46；粒细胞集落刺激因子，n = 51）。在第 5 天 CD34 细胞的采集方面，tbo-粒细胞集落刺激因子不劣于粒细胞集落刺激因子（平均值，11.6±6.7 CD34 细胞/kg 与 10.0±6.8 CD34 细胞/kg）。多变量分析显示 tbo-粒细胞集落刺激因子组有增加动员的趋势，但无统计学意义。tbo-粒细胞集落刺激因子组和粒细胞集落刺激因子组在所有次要终点均相似。在 MM 和 NHL 患者中，与参照粒细胞集落刺激因子相比，tbo-粒细胞集落刺激因子在疗效方面不劣，且安全性相似。在接受 MM 或 NHL 自体 HSCT 的患者中，Granix 可安全替代 Neupogen 用于干细胞采集。该研究在 https://clinicaltrials.gov/ct2/show/NCT02098109 注册。
