Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Pulmonary and Thoracic Oncology Department, Univ Lille, CHU Lille, INSERM U1189 OncoThAI, F59000, Lille, France.
Curr Treat Options Oncol. 2019 Feb 14;20(2):18. doi: 10.1007/s11864-019-0613-x.
Recent advances in immunology have extended into the mesothelioma field. To date, only Japan has given regulatory approval to salvage nivolumab in chemo-refractory mesothelioma patients. The USA has included in the NCCN guidelines that pembrolizumab (in programmed death ligand 1 (PD-L1) immunohistochemistry (IHC)-positive patients) and nivolumab with or without ipilimumab (whatever the PD-L1 status is) are accepted salvage therapies. Based on the growing body of literature, it is anticipated that checkpoint inhibitors will receive regulatory approval in the USA and Europe soon for salvage therapy. Additional research efforts will determine whether earlier stage patients and frontline unresectable patients will benefit from the addition of immunotherapy to their treatment regimens. The realm of biomarker research has lagged behind in mesothelioma. In general, mesothelioma has less tumor mutation burden than other malignancies. Most of the single-agent salvage checkpoint inhibitor trials have shown a trend correlating higher PD-L1 immunohistochemistry (IHC) with responses. However, survival data remains immature and a larger number of patient outcomes are needed to ascertain the value of PD-L1 IHC as a predictive biomarker. Incorporation of translational studies in all immunotherapy trials and especially window-of-opportunity resectable studies should be supported and instituted in all future mesothelioma trials.
免疫学的最新进展已经扩展到间皮瘤领域。迄今为止,只有日本批准了挽救性纳武单抗治疗化疗耐药性间皮瘤患者。美国已将派姆单抗(在程序性死亡配体 1(PD-L1)免疫组织化学(IHC)阳性患者中)和纳武单抗联合或不联合伊匹单抗(无论 PD-L1 状态如何)纳入 NCCN 指南,作为可接受的挽救性治疗。基于不断增加的文献,预计检查点抑制剂将很快在美国和欧洲获得监管部门批准,用于挽救性治疗。进一步的研究将确定早期患者和一线不可切除患者是否会从免疫治疗加入其治疗方案中获益。生物标志物研究在间皮瘤领域一直滞后。一般来说,间皮瘤的肿瘤突变负担低于其他恶性肿瘤。大多数单药挽救性检查点抑制剂试验都显示出一种趋势,即较高的 PD-L1 免疫组织化学(IHC)与反应相关。然而,生存数据仍不成熟,需要更多的患者结局来确定 PD-L1 IHC 作为预测生物标志物的价值。在所有免疫治疗试验中,特别是在机会性可切除研究中,应支持并实施转化研究,这应该在未来所有的间皮瘤试验中得到支持和实施。