Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11–4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.
嵌合抗原受体T细胞(CAR-T)是突破性疗法,但可能引发显著毒性反应,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)以及血细胞减少。粒细胞集落刺激因子(G-CSF)常被用于缓解CAR-T治疗后的中性粒细胞减少,但由于存在可能加重毒性的假设性风险(多数尚未明确),目前尚未形成共识性推荐策略。为探究G-CSF的影响,我们回顾性分析了197例接受抗CD19 CAR-T治疗的淋巴瘤患者和47例接受抗BCMA CAR-T治疗的多发性骨髓瘤患者。在淋巴瘤组中,140例患者(71%)在CAR-T治疗前接受预防性G-CSF(多为聚乙二醇化G-CSF),与57例(29%)在CAR-T治疗后使用或未使用G-CSF的患者进行比较。预防性G-CSF可加速中性粒细胞恢复(3天 vs 4天,P<0.01),但未能减少后期中性粒细胞减少的复发。同时,预防性G-CSF与≥2级CRS发生率升高相关(HR 2.15,95% CI 1.11–4.18,P=0.02),但与ICANS无关。在多发性骨髓瘤组中,未采用预防性G-CSF;根据早期G-CSF暴露时间(CAR-T后≤2天 vs ≥3天或未暴露)进行分层分析,毒性反应未见显著差异。未来需通过临床试验明确G-CSF的最佳使用策略,以改善CAR-T治疗预后。