Dupont R, Bérard E, Puisset F, Comont T, Delord J-P, Guimbaud R, Meyer N, Mazieres J, Alric L
Service de Médecine interne et immunologie clinique, Hôpital Rangueil, CHU de Toulouse, Université Paul Sabatier-Toulouse III, Université de Toulouse, Toulouse, France.
Service d'Epidémiologie, CHU de Toulouse, UMR 1027, INSERM-Université de Toulouse, Toulouse, France.
Oncoimmunology. 2019 Nov 5;9(1):1682383. doi: 10.1080/2162402X.2019.1682383. eCollection 2020.
: Nivolumab and pembrolizumab, two PD1 inhibitors, trigger immune-related adverse events in approximately 50% of patients. Our objective was to determine whether these immune-related adverse events are associated with patient outcomes. : Retrospective cohort study, realized at the , of all the patients treated with nivolumab or pembrolizumab off clinical trials. We included patients (i) diagnosed with unresectable stage III or stage IV melanoma or with recurrent stage IIIB or stage IV non-small cell lung cancer (ii) on nivolumab 3mg/kg or pembrolizumab 2mg/kg every 2 or 3 weeks respectively. : Of the 311 patients included (of 641 eligible subjects), 120 (38.6%) had melanoma and 191 (61.4%) had non-small cell lung cancer; 241 (77.5%) were treated with nivolumab with a median follow-up of 24 months (20-29). We observed 166 immune-related adverse events in 116 (37.3%) patients, categorized as "early" (onset before 12 weeks in melanoma and before 8 weeks in lung cancer) in 63 (54.3%) patients. Early and late adverse events were significantly associated with an increase in overall survival: adjusted hazard ratio 0.58 [0.41-0.84] ( = .003) and 0.28 [0.16-0.50] ( < .001) respectively. The overall response rate was significantly increased in patients with an immune-related adverse event (53.9% vs 12.9%, < .001) : This study validates the association between immune-related adverse events and anti-PD1 efficacy in real-life, especially if these events are delayed. Our results, along with further studies on the place of immunosuppressive drugs in the therapeutic strategy, could improve the management of these adverse events.
纳武单抗和派姆单抗这两种程序性死亡受体1（PD1）抑制剂，在约50%的患者中引发免疫相关不良事件。我们的目的是确定这些免疫相关不良事件是否与患者预后相关。：回顾性队列研究，在所有接受纳武单抗或派姆单抗治疗且未参加临床试验的患者中进行。我们纳入了以下患者：（i）被诊断为不可切除的III期或IV期黑色素瘤或复发性IIIB期或IV期非小细胞肺癌；（ii）分别接受每2周或3周一次3mg/kg纳武单抗或2mg/kg派姆单抗治疗。：在纳入的311例患者（共641例符合条件的受试者）中，120例（38.6%）患有黑色素瘤，191例（61.4%）患有非小细胞肺癌；241例（77.5%）接受了纳武单抗治疗，中位随访时间为24个月（20 - 29个月）。我们在116例（37.3%）患者中观察到166例免疫相关不良事件，其中63例（54.3%）患者的不良事件被归类为“早期”（黑色素瘤患者在12周前发病，肺癌患者在8周前发病）。早期和晚期不良事件均与总生存期延长显著相关：调整后的风险比分别为0.58 [0.41 - 0.84]（P = 0.003）和0.28 [0.16 - 0.50]（P < 0.001）。发生免疫相关不良事件的患者总体缓解率显著提高（53.9%对12.9%，P < 0.001）：本研究证实了免疫相关不良事件与现实生活中抗PD1疗效之间的关联，特别是如果这些事件出现延迟。我们的结果，以及关于免疫抑制药物在治疗策略中地位的进一步研究，可能会改善这些不良事件的管理。
