Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
The First Clinical Medical College, Xuzhou Medical University, Xuzhou, China.
Front Immunol. 2022 Apr 27;13:814548. doi: 10.3389/fimmu.2022.814548. eCollection 2022.
Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory multiple myeloma (R/R MM), the severity of cytokine release syndrome (CRS) can affect patient survival and the risk factors for CRS remain an intractable issue. We enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-B-cell maturation antigen (BCMA) CAR-T cells. The results showed the overall response rate was 94% (51/54) after CAR-T cell infusion, with a 100% incidence of CRS, including 47 patients with grade 1-2 (mild) CRS and 7 patients with grade 3-5 (severe) CRS. In the mild CRS group, the median progression-free survival (PFS) was 18.2 months (95% CI, 6.5 to 30.1) and the median overall survival (OS) was not reached yet. In the severe CRS group, median PFS and median OS were 1.9 months (95% CI, 0.2 to 3.8). Further analysis demonstrated that severe CRS had a shorter median PFS and OS than mild CRS (=0.029, =0.020). Bone marrow tumor burden was found to be independently associated with CRS. The grade of CRS was positively correlated with six serum cytokines levels including G-CSF, IL-6, IL-8, IP-10, MIP-1a and RANTES. In conclusion, early detection and management of CRS are imperative for the prevention of life-threatening complications and improvement in the survival of patients of CAR-T cell therapy.
www.chictr.org.cn, identifier ChiCTR-OIC-17011272.
嵌合抗原受体 T(CAR-T)细胞疗法已被证明在治疗复发或难治性多发性骨髓瘤(R/R MM)方面有效,但细胞因子释放综合征(CRS)的严重程度会影响患者的生存,而 CRS 的危险因素仍然是一个棘手的问题。我们招募了 54 例接受抗 CD19 和抗 B 细胞成熟抗原(BCMA)CAR-T 细胞联合输注的 R/R MM 患者。结果显示,CAR-T 细胞输注后总体缓解率为 94%(51/54),CRS 的发生率为 100%,包括 47 例 1-2 级(轻度)CRS 和 7 例 3-5 级(重度)CRS。在轻度 CRS 组中,中位无进展生存期(PFS)为 18.2 个月(95%CI,6.5-30.1),中位总生存期(OS)尚未达到。在重度 CRS 组中,中位 PFS 和中位 OS 分别为 1.9 个月(95%CI,0.2-3.8)。进一步分析表明,重度 CRS 的中位 PFS 和 OS 短于轻度 CRS(=0.029,=0.020)。骨髓肿瘤负担与 CRS 独立相关。CRS 分级与包括 G-CSF、IL-6、IL-8、IP-10、MIP-1a 和 RANTES 在内的 6 种血清细胞因子水平呈正相关。总之,早期检测和管理 CRS 对于预防危及生命的并发症和改善 CAR-T 细胞治疗患者的生存至关重要。
www.chictr.org.cn,标识符 ChiCTR-OIC-17011272。