Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy.
Immune checkpoint inhibitors in patients with pre-existing psoriasis: safety and efficacy.
复制标题
DOI：
10.1136/jitc-2021-003066
复制
发表时间：
2021-10
影响因子：
10.9
通讯作者：
Rotemberg VM
中科院分区：
文献类型：
--
作者：
Halle BR;Betof Warner A;Zaman FY;Haydon A;Bhave P;Dewan AK;Ye F;Irlmeier R;Mehta P;Kurtansky NR;Lacouture ME;Hassel JC;Choi JS;Sosman JA;Chandra S;Otto TS;Sullivan R;Mooradian MJ;Chen ST;Dimitriou F;Long G;Carlino M;Menzies A;Johnson DB;Rotemberg VM
免疫检查点抑制剂(ICIS)被批准用于治疗多种癌症。回顾分析表明，ICIS在大多数自身免疫性疾病患者中是可以接受的安全性，尽管疾病可能会恶化。寻常型银屑病是一种常见的免疫调节疾病，ICI治疗银屑病患者的结果尚未得到很好的描述。因此，我们试图确定ICIS在既往银屑病患者中的安全性和有效性。在这项回顾性队列研究中，来自8个学术中心的接受ICI癌症治疗的银屑病患者进行了评估。主要的安全结果是牛皮癣恶化和免疫相关不良事件(IrAEs)。我们还评估了无进展生存率(PFS)和总体生存率。在被研究的76例患者中(男性50例(66%)，平均年龄67岁；黑色素瘤62例(82%)，肺癌5例(7%)，头颈部癌2例(3%)，其他癌症7例(9%)；中位随访25.1个月(范围0.2-99个月)，51例(67%)接受抗PD-1抗体，8例(11%)抗CTLA-4，17例(22%)联合应用抗PD-1/CTLA-4。所有患者均有牛皮癣病史，最常见的是斑块型牛皮癣(46例(61%))和15例(20%)牛皮癣关节炎患者。41名患者(54%)以前接受过任何银屑病治疗，但只有两名患者(3%)在ICI开始时接受了全身免疫抑制。接受ICI治疗的43名患者(57%)在接受ICI治疗的中位数为44天后，经历了皮肤和/或皮外疾病的牛皮癣发作。在那些经历了闪光的患者中，23名患者(53%)只接受了局部治疗；16名患者(21%)需要全身治疗。只有5名患者(7%)因银屑病发作而需要停止免疫治疗。45例患者(59%)经历了其他irAEs，其中17例(22%)为3/4级。有标志性分析的银屑病患者的PFS明显长于无银屑病发作的患者(39个月vs8.7个月，p=0.049)。在这项多中心研究中，ICI治疗与牛皮癣的频繁恶化有关，尽管用标准的牛皮癣治疗可以控制红斑，而且很少需要停止ICI。经历过疾病恶化的患者至少表现得和没有经历过的患者一样好。因此，既往存在的银屑病不应阻止患者接受ICIS治疗恶性肿瘤。
Immune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis. In this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We also assessed progression-free survival (PFS) and overall survival. Of 76 patients studied (50 (66%) male; median age 67 years; 62 (82%) with melanoma, 5 (7%) with lung cancer, 2 (3%) with head and neck cancer, and 7 (9%) with other cancers; median follow-up 25.1 months (range=0.2–99 months)), 51 (67%) received anti-PD-1 antibodies, 8 (11%) anti-CTLA-4, and 17 (22%) combination of anti-PD-1/CTLA-4. All patients had pre-existing psoriasis, most frequently plaque psoriasis (46 patients (61%)) and 15 (20%) with psoriatic arthritis. Forty-one patients (54%) had received any prior therapy for psoriasis although only two (3%) were on systemic immunosuppression at ICI initiation. With ICI treatment, 43 patients (57%) experienced a psoriasis flare of cutaneous and/or extracutaneous disease after a median of 44 days of receiving ICI. Of those who experienced a flare, 23 patients (53%) were managed with topical therapy only; 16 (21%) needed systemic therapy. Only five patients (7%) required immunotherapy discontinuation for psoriasis flare. Forty-five patients (59%) experienced other irAEs, 17 (22%) of which were grade 3/4. PFS with landmark analysis was significantly longer in patients with a psoriasis flare versus those without (39 vs 8.7 months, p=0.049). In this multicenter study, ICI therapy was associated with frequent psoriasis exacerbation, although flares were manageable with standard psoriasis treatments and few required ICI discontinuation. Patients who experienced disease exacerbation performed at least as well as those who did not. Thus, pre-existing psoriasis should not prevent patients from receiving ICIs for treatment of malignancy.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
158.5
作者：
Larkin, J.;Chiarion-Sileni, V.;Wolchok, J. D.
通讯作者：
Wolchok, J. D.
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
影响因子：
51.1
作者：
Johnson, Douglas B.;Reynolds, Kerry L.;Moslehi, Javid J.
通讯作者：
Moslehi, Javid J.