CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Case Report: Severe cutaneous adverse event associated with checkpoint inhibition in the setting of CAR T-cell therapy: beyond CRS.
Case Report: Severe cutaneous adverse event associated with checkpoint inhibition in the setting of CAR T-cell therapy: beyond CRS.
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抗CD19嵌合抗原受体(CAR)T细胞疗法实际上已成为多发性复发/难治性原发性纵隔B细胞淋巴瘤(r/r PMBCL)的标准治疗。对于不适合或对自体干细胞移植耐药的患者,诸如pembrolizumab等检查点抑制剂似乎是一种安全有效的治疗策略。尽管临床前研究表明检查点抑制剂可能增强CAR-T 细胞的活力和抗肿瘤活性,但关于二者联合应用所引发的免疫介导毒性的实质性/稳健临床数据尚缺乏。
我们描述了一例年轻r/r PMBCL患者在接受CAR-T 细胞输注后第+6天,于细胞因子释放综合征(CRS)之后立即出现的严重皮肤不良事件,该患者此前曾接受过pembrolizumab治疗。考虑到在全身类固醇治疗基础上加用免疫球蛋白输注后皮损迅速改善并完全恢复,这些皮肤病变被判定为免疫介导的不良事件。这例危及生命的皮肤不良事件呼吁进一步研究CAR-T 细胞疗法与检查点抑制联合应用所产生的脱靶免疫相关不良事件,而二者的协同治疗效果前景可观。
Anti-CD19 chimeric antigen receptor (CAR) T cell therapy actually represents the standard of care for multiple relapsed or refractory primary mediastinal B-cell lymphoma (r/r PMBCL). Checkpoint inhibitors, such as pembrolizumab, appear to be a safe and effective treatment strategy for patients who are ineligible for or resistant to autologous stem cell transplantation.
Although preclinical studies suggested that checkpoint inhibitors may enhance the vitality and anti-tumor activity of CAR T cells, there are no substantial/robust clinical data about the immune-mediated toxicity of their association.
We describe a case of a severe cutaneous adverse event arising immediately after Cytokine Release Syndrome (CRS) on day +6 from CAR T cells infusion in a young r/r PMBCL patient who previously received pembrolizumab. These skin lesions were interpreted as an immune mediated adverse event, considering their prompt improvement and fully recovering achieved with the addition of immunoglobulin infusion to systemic steroid therapy.
This case of life-threatening cutaneous adverse event calls for further investigations about off-target immune-related adverse events deriving from the combination of CAR T cell therapy and checkpoint inhibition, whose synergic therapeutic effect is promising.
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