Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Expert Opin Drug Saf. 2020 Apr;19(4):409-421. doi: 10.1080/14740338.2020.1757068.
: Due to its unique mechanism of action as an immune checkpoint inhibitor, nivolumab has high antitumor activity, but at the same time this mechanism is responsible for immune-related adverse events that may limit patients' safety and therapy continuation.: Long-term safety of nivolumab including 5-year follow-up, safety of nivolumab treatment after ipilimumab therapy, safety of nivolumab in challenging subgroups (elderly, patients with brain metastases, patients with autoimmune disorders), safety of nivolumab in with rare melanoma subtypes (including mucosal melanoma), as well as specificity of AEs reported for nivolumab treatment in melanoma patients in comparison to other cancer types and other immunotherapy molecules, and impact of AEs on response rates and PFS on nivolumab treatment are discussed.: Search for biomarkers that would help us to identify patient populations that may suffer from severe nivolumab toxicity could help in selecting patients that should not be treated with this type of therapy. Novel combinations and immunotherapy drugs including use of NKTR-214 (IL-2 pathway), lymphocyte-activation gene 3 (LAG-3), local injections of talimogene laherparepvec (T-VEC), or systemic use of T-cell receptors agonists such as OX40, CD137, ICOS-1, could provide regimens with limited toxicity and higher activity.
由于其作为免疫检查点抑制剂的独特作用机制，纳武利尤单抗具有很高的抗肿瘤活性，但同时，这种机制也导致了免疫相关的不良反应，可能限制了患者的安全性和治疗的持续时间。
包括 5 年随访在内的纳武利尤单抗的长期安全性、纳武利尤单抗治疗后伊匹单抗治疗的安全性、纳武利尤单抗在挑战性亚组（老年、脑转移患者、自身免疫性疾病患者）中的安全性、纳武利尤单抗在罕见黑色素瘤亚型（包括黏膜黑色素瘤）中的安全性，以及与其他癌症类型和其他免疫治疗药物相比，黑色素瘤患者中报告的纳武利尤单抗治疗的不良反应的特异性，以及不良反应对纳武利尤单抗治疗的反应率和无进展生存期的影响。
寻找有助于我们识别可能发生严重纳武利尤单抗毒性的患者人群的生物标志物，可能有助于选择不应接受这种治疗类型的患者。新型联合用药和免疫治疗药物，包括使用 NKTR-214（IL-2 途径）、淋巴细胞激活基因 3（LAG-3）、局部注射替西利珠单抗（T-VEC）或全身使用 T 细胞受体激动剂，如 OX40、CD137、ICOS-1，可能提供毒性有限、活性更高的治疗方案。
