决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Cutaneous Toxicities of T-Cell-Redirecting Therapies in Multiple Myeloma: An EADV Task Force Position Paper and Practical Recommendations.
Cutaneous Toxicities of T-Cell-Redirecting Therapies in Multiple Myeloma: An EADV Task Force Position Paper and Practical Recommendations.
T细胞重定向免疫疗法,包括双特异性抗体和嵌合抗原受体(CAR)T细胞疗法,已迅速成为复发或难治性多发性骨髓瘤的主要治疗选择,但与一系列独特的皮肤毒性相关。
T细胞重定向免疫疗法,包括双特异性抗体和嵌合抗原受体(CAR)T细胞疗法,已迅速成为复发或难治性多发性骨髓瘤的主要治疗选择,但与一组独特的皮肤毒性谱相关。皮肤表现在靶向GPRC5D的药物中尤为突出,反映了针对硬角化组织的靶向、脱肿瘤活性,而靶向BCMA的双特异性抗体和抗BCMA CAR T细胞疗法相关的皮肤不良事件则较轻且表型特征较不明显。尽管具有临床相关性,这些毒性的报告仍不一致,且缺乏标准化定义和管理策略。本欧洲皮肤病与性病学会(EADV)"癌症患者皮肤病学"工作组立场文件,与具有多发性骨髓瘤诊疗经验的血液科单位合作制定,综述了与T细胞重定向疗法相关的皮肤毒性的机制基础、临床谱和分级。我们提出一个以表型驱动的阶梯式管理框架,围绕4种主要模式——屏障功能障碍与角化过度性疾病、炎症性皮肤 eruption、甲毒性及注射部位反应——整合预防策略、基线皮肤评估和按分级调整的治疗算法。
T-cell-redirecting immunotherapies, including bispecific antibodies and chimeric antigen receptor (CAR) T-cell therapies, have rapidly become major treatment options of relapsed or refractory multiple myeloma but are associated with a distinctive spectrum of cutaneous toxicities. Dermatologic manifestations are particularly prominent with GPRC5D-targeting agents, reflecting on-target, off-tumor activity against hard-keratinizing tissues, whereas BCMA-targeted bispecific antibodies and anti-BCMA CAR T-cell therapies are associated with milder and less phenotypically distinct cutaneous adverse events. Despite their clinical relevance, these toxicities remain inconsistently reported, and standardized definitions and management strategies are lacking. This European Academy of Dermatology and Venereology (EADV) Task Force "Dermatology for Cancer Patients" position paper, developed in collaboration with hematology units experienced in multiple myeloma care, reviews the mechanistic basis, clinical spectrum, and grading of cutaneous toxicities associated with T-cell-redirecting therapies. We propose a phenotype-driven, stepwise management framework organized around 4 principal patterns - barrier dysfunction and hyperkeratotic disease, inflammatory cutaneous eruptions, nail toxicity, and injection-site reactions- incorporating preventive strategies, baseline dermatologic assessment, and grade-adapted treatment algorithms.
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