Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy.
Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy.
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DOI：
10.1016/j.bbmt.2019.06.036
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Locke FL
中科院分区：
文献类型：
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作者：
Byrne M;Oluwole OO;Savani B;Majhail NS;Hill BT;Locke FL
大多数大细胞淋巴瘤患者通过一线化疗免疫治疗得以治愈。对于难治性疾病患者和那些在常规治疗后复发的患者，嵌合抗原受体(CAR)T细胞是一种重要的治疗选择，并已导致其他难治性患者的缓解。在关键试验中，大约40%到50%的患者在接受axicabagene cilolucel、tisagenlecleucel或lisocabagene maraleucel治疗时取得了持久的疗效，这表明许多患者将需要后续治疗。CAR T细胞治疗失败是由多种因素引起的，这些因素可分为三大类：肿瘤内在因素、其他宿主因素和CAR T细胞不足。在这个框架内，本文回顾了治疗失败的可能机制，并基于复发的时间，考虑了潜在的挽救疗法和未来临床研究的机会。
Most patients with large cell lymphoma are cured with frontline chemoimmunotherapy. For individuals with refractory disease and those who relapse after conventional therapies, chimeric antigen receptor (CAR) T cells are an important treatment option and have led to remissions in otherwise refractory patients. In the pivotal trials, durable responses were achieved in approximately 40% to 50% of patients treated with axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel, indicating that many patients will require subsequent treatment. Failure after CAR T cell therapy is caused by a variety of factors that can be divided into 3 broad categories: tumor intrinsic factors, other host factors, and inadequacies of the CAR T cells. Within this framework, this article reviews possible mechanisms of treatment failures and, based on the timing of relapse, considers potential salvage therapies and opportunities for future clinical studies.