■B细胞成熟抗原(BCMA)靶向的嵌合抗原受体T细胞(CAR-T)疗法用于难治性或复发性多发性骨髓瘤(r/rMM)。然而,已经观察到CAR-T相关的肿瘤溶解综合征(TLS)。我们旨在阐明发病率,临床和实验室特征,CAR-T细胞相关TLS的预后。
■包括用BCMA靶向CAR-T细胞疗法治疗的r/rMM患者(n=105)。患者特征,实验室参数,并对临床结局进行评估.
■18例(17.1%)患者在BCMA靶向CAR-T细胞治疗后出现TLS。TLS发病的中位时间为8天。TLS患者的尿酸(UA)急剧上升,肌酐,和乳酸脱氢酶(LDH)在CAR-T细胞输注后6天内,并呈现较早和持续的细胞因子升级(C反应蛋白[CRP],白细胞介素-6[IL-6],干扰素-γ[IFN-γ],和铁蛋白水平)。18例患者均有细胞因子释放综合征(CRS),其中13人(72.2%)发展为3-4级CRS。18例患者中有3例(16.7%)出现免疫效应细胞相关神经毒性综合征(ICANS):2例1级ICANS患者和1例2级ICANS患者。TLS开发对客观反应率有负面影响(TLS组中77.8%与非TLS组中的95.4%,p<0.01)。在15.1个月的中位随访期间,TLS患者的中位PFS较差(中位数:TLS组的3.4个月与在非TLS组中14.7个月,p<0.001,风险比[HR]=3.5[95%置信区间[CI]1.5-8.5])。此外,TLS开发对OS表现出显着影响(中位数:TLS组5.0个月与非TLS组39.8个月,p<0.001,风险比[HR]=3.7[95%CI1.3-10.3])。TLS与更高的肿瘤负担相关,基线肌酐和UA水平升高,严重CRS,明显的CAR-T细胞扩增,和皮质类固醇的使用。
■TLS是经常观察到的CAR-T治疗并发症,对临床反应和预后产生负面影响。在CAR-T细胞治疗期间应密切监测TLS,特别是对于那些高TLS风险的人。
B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T cell (CAR-T) therapy is used for refractory or relapsed multiple myeloma (r/r MM). However, CAR-T-related tumor lysis syndrome (TLS) has been observed. We aimed to elucidate the incidence, clinical and laboratory characteristics, and prognosis of CAR-T cell-related TLS.
Patients (n=105) with r/r MM treated with BCMA-targeted CAR-T cell therapy were included. Patient characteristics, laboratory parameters, and clinical outcomes were assessed.
Eighteen (17.1%) patients developed TLS after BCMA-targeted CAR-T cell therapy. The median time till TLS onset was 8 days. Patients with TLS had steep rise in uric acid (UA), creatinine, and lactate dehydrogenase (LDH) within 6 days following CAR-T cell infusion and presented earlier and persistent escalation of cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-γ [IFN-γ], and ferritin levels). All 18 patients had cytokine release syndrome (CRS), of which 13 (72.2%) developed grade 3-4 CRS. Three of 18 patients (16.7%) developed immune effector cell-associated neurotoxicity syndrome (ICANS): two patients with grade 1 ICANS and one with grade 2 ICANS. TLS development had a negative effect on the objective response rate (77.8% in the TLS group vs. 95.4% in the non-TLS group, p<0.01). During the median follow-up of 15.1 months, the median PFS was poorer of patients with TLS (median: 3.4 months in the TLS group vs. 14.7 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.5 [95% confidence interval [CI] 1.5-8.5]). Also, TLS development exhibited significant effects on OS (median: 5.0 months in the TLS group vs. 39.8 months in the non-TLS group, p<0.001, hazard ratio [HR]=3.7 [95% CI 1.3-10.3]). TLS was associated with a higher tumor burden, elevated baseline creatinine and UA levels, severe CRS, pronounced CAR-T cell expansion, and corticosteroid use.
TLS is a frequently observed CAR-T therapy complication and negatively influences clinical response and prognosis. Close monitoring for TLS should be implemented during CAR-T cell therapy, especially for those at high TLS risk.