Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab.
Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor-induced enterocolitis treated with infliximab.
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DOI：
10.1136/jitc-2021-002742
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发表时间：
2021-07
影响因子：
10.9
通讯作者：
Powell N
中科院分区：
文献类型：
--
作者：
Alexander JL;Ibraheim H;Sheth B;Little J;Khan MS;Richards C;Hunter N;Chauhan D;Ratnakumaran R;McHugh K;Pinato DJ;Nathan P;Choy J;Crusz SM;Furness A;Turajlic S;Pickering L;Larkin J;Teare JP;Papa S;Speight A;Sharma A;Powell N
免疫检查点抑制剂（CPI）已经改变了许多癌症的治疗前景，但也会引起严重的炎症副作用，包括小肠结肠炎。CPI诱导的小肠结肠炎经验性地用皮质类固醇治疗，英夫利昔单抗（IFX）用于皮质类固醇难治性病例。然而，这些患者的可靠结果数据很少。我们对2007年至2020年期间接受IFX治疗的皮质类固醇难治性CPI诱导的小肠结肠炎患者的结局进行了多中心（6个癌症中心）队列研究。主要结局是IFX开始后12周时腹泻无糖皮质激素临床缓解（CFCR），不良事件通用术语标准（CTCAE）为0级。我们还使用RECIST V1.1标准评估了1年时的癌症结局。127例患者（73例男性;中位年龄59岁）接受IFX治疗皮质类固醇难治性CPI诱导的小肠结肠炎。96例（75.6%）患者出现CTCAE>2级腹泻，115例（90.6%）患者因结肠炎需要住院治疗。12周时CFCR为41.2%，26周时为50.9%。在多变量逻辑回归中，IFX耐药小肠结肠炎与直肠出血（OR 0.19; 95%CI 0.04至0.80; p=0.03）和无结肠隐窝脓肿（OR 2.16; 95%CI 1.13至8.05; p=0.03）相关。与IFX应答性小肠结肠炎患者（37.5%; p=0.013）相比，IFX耐药小肠结肠炎患者（64.4%）的癌症非进展显著更常见。这是迄今为止报告IFX治疗皮质类固醇难治性CPI诱导的小肠结肠炎患者结局的最大规模研究。使用预定义的稳健终点，我们已经证明只有不到一半的患者达到CFCR。我们的数据还表明，CPI治疗的长期和严重炎症副作用患者的癌症结局可能更好。
Immune checkpoint inhibitors (CPIs) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. We conducted a multicenter (six cancer centers), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with Common Terminology Criteria for Adverse Events (CTCAE) grade 0 for diarrhea at 12 weeks after IFX initiation. We also assessed cancer outcomes at 1 year using RECIST V1.1 criteria. 127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhea CTCAE grade >2 and 115 (90.6%) required hospitalization for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistic regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04 to 0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13 to 8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared with patients with IFX-responsive enterocolitis (37.5%; p=0.013). This is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Using predefined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI therapy.
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影响因子：
10.9
作者：
Johnson DH;Zobniw CM;Trinh VA;Ma J;Bassett RL Jr;Abdel-Wahab N;Anderson J;Davis JE;Joseph J;Uemura M;Noman A;Abu-Sbeih H;Yee C;Amaria R;Patel S;Tawbi H;Glitza IC;Davies MA;Wong MK;Woodman S;Hwu WJ;Hwu P;Wang Y;Diab A
通讯作者：
Diab A
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8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
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Verweij, J.
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Fidder, H.;Schnitzler, F.;Rutgeerts, P.
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Rutgeerts, P.
影响因子：
29.4
作者：
Long MD;Martin CF;Pipkin CA;Herfarth HH;Sandler RS;Kappelman MD
通讯作者：
Kappelman MD
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10.9
作者：
Abu-Sbeih H;Ali FS;Luo W;Qiao W;Raju GS;Wang Y
通讯作者：
Wang Y