Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Cancer Institute, Xuzhou Medical University, Xuzhou, China; Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Cytotherapy. 2023 Jun;25(6):653-658. doi: 10.1016/j.jcyt.2023.01.011. Epub 2023 Mar 11.
Few studies have reported the associations of granulocyte colony-stimulating factor (G-CSF) with cytokine release syndrome (CRS), neurotoxic events (NEs) and efficacy after chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) multiple myeloma (MM). We present a retrospective study performed on 113 patients with R/R MM who received single anti-BCMA CAR T-cell, combined with anti-CD19 CAR T-cell or anti-CD138 CAR T-cell therapy.
Eight patients were given G-CSF after successful management of CRS, and no CRS re-occurred thereafter. Of the remaining 105 patients that were finally analyzed, 72 (68.6%) received G-CSF (G-CSF group), and 33 (31.4%) did not (non G-CSF group). We mainly analyzed the incidence and severity of CRS or NEs in two groups of patients, as well as the associations of G-CSF timing, cumulative dose and cumulative time with CRS, NEs and efficacy of CAR T-cell therapy.
Both groups of patients had similar duration of grade 3-4 neutropenia, and the incidence and severity of CRS or NEs.There were also no differences in the incidence and severity of CRS or NEs between patients with the timing of G-CSF administration ≤3 days and those >3 days after CAR T-cell infusion. The incidence of CRS was greater in patients receiving cumulative doses of G-CSF >1500 μg or cumulative time of G-CSF administration >5 days. Among patients with CRS, there was no difference in the severity of CRS between patients who used G-CSF and those who did not. The duration of CRS in anti-BCMA and anti-CD19 CAR T-cell-treated patients was prolonged after G-CSF administration. There were no significant differences in the overall response rate at 1 and 3 months between the G-CSF group and the non-G-CSF group.
Our results showed that low-dose or short-time use of G-CSF was not associated with the incidence or severity of CRS or NEs, and G-CSF administration did not influence the antitumor activity of CAR T-cell therapy.
很少有研究报告粒细胞集落刺激因子(G-CSF)与细胞因子释放综合征(CRS)、神经毒性事件(NEs)和嵌合抗原受体(CAR)T 细胞治疗复发或难治性(R/R)多发性骨髓瘤(MM)的疗效之间的关系。我们报告了一项对 113 例接受单克隆抗 BCMA CAR T 细胞、联合抗 CD19 CAR T 细胞或抗 CD138 CAR T 细胞治疗的 R/R MM 患者进行的回顾性研究。
8 例患者在成功管理 CRS 后给予 G-CSF,此后未再发生 CRS。在最终分析的 105 例患者中,72 例(68.6%)接受了 G-CSF(G-CSF 组),33 例(31.4%)未接受(非 G-CSF 组)。我们主要分析了两组患者 CRS 或 NEs 的发生率和严重程度,以及 G-CSF 时机、累积剂量和累积时间与 CRS、NEs 和 CAR T 细胞治疗疗效的关系。
两组患者的 3-4 级中性粒细胞减少持续时间相似,CRS 或 NEs 的发生率和严重程度也相似。CAR T 细胞输注后 G-CSF 给药时间≤3 天和>3 天的患者之间,CRS 或 NEs 的发生率和严重程度也无差异。G-CSF 累积剂量>1500μg 或 G-CSF 给药时间>5 天的患者,CRS 发生率较高。CRS 患者中,使用 G-CSF 与未使用 G-CSF 的患者 CRS 严重程度无差异。抗 BCMA 和抗 CD19 CAR T 细胞治疗患者在 G-CSF 给药后 CRS 持续时间延长。G-CSF 组和非 G-CSF 组在 1 个月和 3 个月的总缓解率无显著差异。
我们的结果表明,低剂量或短时间使用 G-CSF 与 CRS 或 NEs 的发生率或严重程度无关,G-CSF 给药不影响 CAR T 细胞治疗的抗肿瘤活性。