Tudesq Jean-Jacques, Yakoub-Agha Mathilde, Bay Jacques-Olivier, Courbon Corinne, Paul Franciane, Picard Muriel, Pochon Cécile, Sterin Arthur, Vicente Céline, Canet Emmanuel, Yakoub-Agha Ibrahim, Moreau Anne-Sophie
CHU Montpellier, université Montpellier, département d'hématologie clinique, Montpellier, France.
CHU d'Amiens, service de réanimation médicale, Amiens, France.
Bull Cancer. 2023 Feb;110(2S):S116-S122. doi: 10.1016/j.bulcan.2021.11.002. Epub 2021 Dec 8.
The use of chimeric antigen receptor T cells (CAR-T) has increased since their approval in the treatment of several relapsed/refractory B cell malignancies. The management of their specific toxicities, such as cytokine release syndrome (CRS), tends to be better understood and well-defined. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on the management of patients developing CRS following CAR-T cell therapy. A special chapter has been allocated to macrophage activation syndrome (MAS), a rare but life-threatening complication post-CAR-T. In addition to symptomatic measures and preemptive broad-spectrum antibiotics, immunomodulators such as tocilizumab and corticosteroids remain the corner stone for the treatment of CRS. Tocilizumab/corticosteroids-resistant CRS associated with haemophagocytosis markers (spleen and liver enlargement, hyperferritinaemia>10,000ng/mL, hypofibrinogenemia…) should direct the diagnosis towards an overlapping CRS/MAS. An adapted treatment will be based on high-dose IV anakinra and corticosteroids and chemotherapy with etoposide at late refractory stages. These complications and others delignate the need of close collaboration with an intensive care unit.
自嵌合抗原受体T细胞(CAR-T)被批准用于治疗几种复发/难治性B细胞恶性肿瘤以来,其使用量有所增加。对其特定毒性的管理,如细胞因子释放综合征(CRS),往往得到了更好的理解和明确的界定。在法语国家骨髓移植和细胞治疗协会(SFGM-TC)第十二版实践协调研讨会上,一个工作组将工作重点放在了CAR-T细胞治疗后发生CRS的患者的管理上。有一个专门的章节介绍了巨噬细胞活化综合征(MAS),这是一种CAR-T治疗后罕见但危及生命的并发症。除了对症措施和预防性使用广谱抗生素外,托珠单抗和皮质类固醇等免疫调节剂仍然是治疗CRS的基石。与噬血细胞标记物(脾脏和肝脏肿大、高铁蛋白血症>10,000ng/mL、低纤维蛋白原血症……)相关的托珠单抗/皮质类固醇耐药CRS应将诊断导向重叠的CRS/MAS。适应性治疗将基于大剂量静脉注射阿那白滞素和皮质类固醇,以及在晚期难治阶段使用依托泊苷进行化疗。这些并发症以及其他情况表明需要与重症监护病房密切合作。