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Association of Anti-TNF with Decreased Survival in Steroid Refractory Ipilimumab and Anti-PD1-Treated Patients in the Dutch Melanoma Treatment Registry.
Clinical Cancer Research ( IF 11.5 ) Pub Date : 2020-05-01 , DOI: 10.1158/1078-0432.ccr-19-3322
Rik J Verheijden 1 , Anne M May 2 , Christian U Blank 3 , Maureen J B Aarts 4 , Franchette W P J van den Berkmortel 5 , Alfonsus J M van den Eertwegh 6 , Jan Willem B de Groot 7 , Marye J Boers-Sonderen 8 , Jacobus J M van der Hoeven 8 , Geke A Hospers 9 , Djura Piersma 10 , Rozemarijn S van Rijn 11 , Albert J Ten Tije 12 , Astrid A M van der Veldt 13 , Gerard Vreugdenhil 14 , Michiel C T van Zeijl 15 , Michel W J M Wouters 3 , John B A G Haanen 16 , Ellen Kapiteijn 17 , Karijn P M Suijkerbuijk 1
Affiliation  

PURPOSE Unleashing the immune system by PD-1 and/or CTLA-4 blockade can cause severe immune-related toxicity necessitating immunosuppressive treatment. Whether immunosuppression for toxicity impacts survival is largely unknown. EXPERIMENTAL DESIGN Using data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR), we analyzed the association between severe toxicity and overall survival (OS) in 1,250 patients with advanced melanoma who were treated with immune checkpoint inhibitors (ICI) in first line between 2012 and 2017. Furthermore, we analyzed whether toxicity management affected survival in these patients. RESULTS A total of 1,250 patients were included, of whom 589 received anti-PD1 monotherapy, 576 ipilimumab, and 85 combination therapy. A total of 312 patients (25%) developed severe (grade ≥3) toxicity. Patients experiencing severe ICI toxicity had a significantly prolonged survival with a median OS of 23 months compared with 15 months for patients without severe toxicity [hazard ratio (HRadj) = 0.77; 95% confidence interval (CI), 0.63-0.93]. Among patients experiencing severe toxicity, survival was significantly decreased in patients who received anti-TNF ± steroids for steroid-refractory toxicity compared with patients who were managed with steroids only (HRadj = 1.61; 95% CI, 1.03-2.51), with a median OS of 17 and 27 months, respectively. CONCLUSIONS Patients experiencing severe ICI toxicity have a prolonged OS. However, this survival advantage is abrogated when anti-TNF is administered for steroid-refractory toxicity. Further prospective studies are needed to assess the effect of different immunosuppressive regimens on checkpoint inhibitor efficacy.See related commentary by Weber and Postow, p. 2085.

中文翻译:

在荷兰黑素瘤治疗注册中心,类固醇难治性伊立木单抗和抗PD1治疗的患者中抗TNF与存活率降低的关联。

目的通过PD-1和/或CTLA-4阻断释放免疫系统会引起严重的免疫相关毒性,因此有必要进行免疫抑制治疗。免疫抑制毒性是否会影响存活率尚不清楚。实验设计使用来自全国前瞻性的荷兰黑素瘤治疗注册机构(DMTR)的数据,我们分析了2012年第一线接受免疫检查点抑制剂(ICI)治疗的1,250例晚期黑素瘤患者的严重毒性与总生存(OS)的相关性和2017年。此外,我们分析了毒性管理是否影响这些患者的生存。结果共纳入1,250例患者,其中589例接受抗PD1单药治疗,576例伊立木单抗和85例联合治疗。共有312名患者(25%)出现严重(≥3级)毒性。发生严重ICI毒性的患者的生存期显着延长,中位OS​​为23个月,而没有严重毒性的患者则为15个月[危险比(HRadj)= 0.77; 95%置信区间(CI),0.63-0.93]。在发生严重毒性的患者中,接受抗TNF±类固醇抗类固醇难治性毒性的患者的生存率与仅接受类固醇的患者相比显着降低(HRadj = 1.61; 95%CI,1.03-2.51),中位数OS分别为17个月和27个月。结论发生严重ICI毒性的患者的OS延长。但是,当给予抗TNF类固醇难治性毒性时,这种生存优势就被取消了。还需要进一步的前瞻性研究来评估不同的免疫抑制方案对检查点抑制剂疗效的影响。2085。
更新日期:2020-05-01
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