Clinical characterization of colitis arising from anti-PD-1 based therapy

被引：52

作者：

Wang, Daniel Y. ^{[1
]}

Mooradian, Meghan J. ^{[2
]}

Kim, DaeWon ^{[3
]}

Shah, Neil J. ^{[4
]}

Fenton, Sarah E. ^{[5
]}

Conry, Robert M. ^{[6
]}

Mehta, Rutika ^{[7
]}

Silk, Ann W. ^{[8
]}

Zhou, Alice ^{[1
]}

Compton, Margaret L. ^{[9
]}

Al-Rohil, Rami N. ^{[9
]}

Lee, Sunyoung ^{[7
]}

Voorhees, Amber L. ^{[3
]}

Ha, Lisa ^{[5
]}

McKee, Svetlana ^{[6
]}

Norrell, Jacqueline T. ^{[8
]}

Mehnert, Janice ^{[8
]}

Puzanov, Igor ^{[7
]}

Sosman, Jeffrey A. ^{[5
]}

Chandra, Sunandana ^{[5
]}

Gibney, Geoffrey T. ^{[4
]}

Rapisuwon, Suthee ^{[4
]}

Eroglu, Zeynep ^{[3
]}

Sullivan, Ryan ^{[2
]}

Johnson, Douglas B. ^{[1
]}

机构：

[1] Vanderbilt Univ, Dept Med, Nashville, TN USA

[2] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Med, Tampa, FL USA

[4] Georgetown Univ, Dept Med, Lombardi Canc Ctr, Washington, DC USA

[5] Northwestern Univ, Dept Med, Chicago, IL 60611 USA

[6] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[7] Roswell Pk Canc Inst, Dept Med, Buffalo, IL USA

[8] Rutgers Canc Inst New Jersey, Dept Med, New Brunswick, NJ USA

[9] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA

来源：

ONCOIMMUNOLOGY | 2019年 / 8卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Colitis; immune-related adverse events; anti-programmed-death-1; immunotherapy; melanoma; METASTATIC MELANOMA; ADVERSE EVENTS; STAGE-III; IPILIMUMAB; NIVOLUMAB; ANTI-CTLA-4; TOXICITIES; SURVIVAL;

D O I：

10.1080/2162402X.2018.1524695

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy ("monotherapy") or combined with ipilimumab ("combination therapy") were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.

引用

页数：8