Department of Medicine, Cellular Therapy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Blood Cancer J. 2024 May 27;14(1):84. doi: 10.1038/s41408-024-01048-0.
Despite being the mainstay of management for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), there is limited data regarding the impact of tocilizumab (TCZ) and corticosteroids (CCS) on chimeric antigen receptor (CAR) T-cell efficacy in multiple myeloma (MM). The present study aims to evaluate the prognostic impact of these immunosuppressants in recipients of BCMA- or GPRC5D-directed CAR T cells for relapsed/refractory MM. Our retrospective cohort involved patients treated with commercial or investigational autologous CAR T-cell products at a single institution from March 2017-March 2023. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response rate (CRR), and overall survival (OS). In total, 101 patients (91% treated with anti-BCMA CAR T cells and 9% treated with anti-GPRC5D CAR T cells) were analyzed. Within 30 days post-infusion, 34% received CCS and 49% received TCZ for CRS/ICANS management. At a median follow-up of 27.4 months, no significant difference in PFS was observed between CCS and non-CCS groups (log-rank p = 0.35) or between TCZ and non-TCZ groups (log-rank p = 0.69). ORR, CRR, and OS were also comparable between evaluated groups. In our multivariable model, administering CCS with/without TCZ for CRS/ICANS management did not independently influence PFS (HR, 0.74; 95% CI, 0.36-1.51). These findings suggest that, among patients with relapsed/refractory MM, the timely and appropriate use of CCS or TCZ for mitigating immune-mediated toxicities does not appear to impact the antitumor activity and long-term outcomes of CAR T-cell therapy.
尽管托珠单抗(TCZ)和皮质类固醇(CCS)是细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)管理的主要手段,但关于它们对多发性骨髓瘤(MM)中嵌合抗原受体(CAR)T 细胞疗效的影响的数据有限。本研究旨在评估这些免疫抑制剂在接受 BCMA 或 GPRC5D 定向 CAR T 细胞治疗复发性/难治性 MM 患者中的预后影响。我们的回顾性队列包括 2017 年 3 月至 2023 年 3 月期间在一家机构接受商业或研究性自体 CAR T 细胞产品治疗的患者。主要终点是无进展生存期(PFS)。次要终点包括总缓解率(ORR)、完全缓解率(CRR)和总生存期(OS)。共有 101 例患者(91%接受抗-BCMA CAR T 细胞治疗,9%接受抗-GPRC5D CAR T 细胞治疗)被纳入分析。在输注后 30 天内,34%的患者因 CRS/ICANS 管理接受 CCS,49%的患者接受 TCZ。在中位随访 27.4 个月时,CCS 组和非 CCS 组之间的 PFS 无显著差异(对数秩检验 p=0.35),TCZ 组和非 TCZ 组之间也无显著差异(对数秩检验 p=0.69)。评估组之间的 ORR、CRR 和 OS 也相似。在我们的多变量模型中,CCS 联合/不联合 TCZ 用于 CRS/ICANS 管理并不会独立影响 PFS(HR,0.74;95%CI,0.36-1.51)。这些发现表明,在复发性/难治性 MM 患者中,及时、适当使用 CCS 或 TCZ 缓解免疫介导的毒性似乎不会影响 CAR T 细胞治疗的抗肿瘤活性和长期结局。