Diagnostic Comparison of CT Scans and Colonoscopy for Immune-Related Colitis in Ipilimumab-Treated Advanced Melanoma Patients

Checkpoint blockade is becoming more widespread, so the timely and accurate diagnosis of immune-related colitis is increasingly important. By comparing diagnoses with colonoscopy data, CT scans were a fast, accurate, and non invasive mode of diagnosing ipilimumab-induced immune-related colitis. Colitis can be a life-threatening toxicity for patients treated with immune checkpoint blockade antibodies. With the anticipated widespread use of these reagents, the timely and accurate diagnosis of immune-related colitis becomes increasingly important. To better understand the clinical presentation of colitis from ipilimumab and to assess the use of CT scans of the abdomen/pelvis as a diagnostic tool, we retrospectively analyzed patients with advanced melanoma who received ipilimumab at our institution. Ninety nine (33%) of 303 patients developed diarrhea during therapy, and 46 patients (15%) received corticosteroids for colitis. Of the patients with diarrhea, 48 (48%) underwent colonoscopy and 46 (46%) underwent both CT and colonoscopy. In the 34 patients (34%) with a CT and biopsy, CT was highly predictive of colitis on biopsy (positive predictive value 96%), and the absence of CT findings was predictive of a negative biopsy (negative likelihood ratio 0.2). In patients who had symptoms and CT evaluation, CT was highly predictive of the need for steroids to reach resolution of symptoms (positive predictive value 92%, positive likelihood ratio 7.3). We conclude that CT is a fast, reliable, and noninvasive mode of diagnosing colitis, whereas colonoscopy and biopsy may not be needed to establish that diagnosis. Cancer Immunol Res; 5(4); 286–91. ©2017 AACR.

[1]  L. Molinero,et al.  The composition of the microbiota modulates allograft rejection. , 2016, The Journal of clinical investigation.

[2]  C. Huttenhower,et al.  Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis , 2016, Nature Communications.

[3]  F. Ginhoux,et al.  Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota , 2015, Science.

[4]  Jason B. Williams,et al.  Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy , 2015, Science.

[5]  M. Valsecchi Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. , 2015, The New England journal of medicine.

[6]  G. Linette,et al.  Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. , 2015, The New England journal of medicine.

[7]  P. Sharma,et al.  The future of immune checkpoint therapy , 2015, Science.

[8]  J. Kench,et al.  Ipilimumab‐induced toxicities and the gastroenterologist , 2015, Journal of gastroenterology and hepatology.

[9]  D. Schadendorf,et al.  Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  J. Kirkwood,et al.  Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. , 2014, JAMA.

[11]  F. Hodi,et al.  Ipilimumab and its toxicities: a multidisciplinary approach. , 2013, The oncologist.

[12]  A. Shinagare,et al.  Ipilimumab-associated colitis: CT findings. , 2013, AJR. American journal of roentgenology.

[13]  A. Hauschild,et al.  Management of immune-related adverse events and kinetics of response with ipilimumab. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Axel Hoos,et al.  Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. , 2011, The New England journal of medicine.

[15]  M. Kagnoff,et al.  GM-CSF: a role in immune and inflammatory reactions in the intestine , 2010, Expert review of gastroenterology & hepatology.

[16]  D. Schadendorf,et al.  Improved survival with ipilimumab in patients with metastatic melanoma. , 2010, The New England journal of medicine.

[17]  Jing Jing Li,et al.  A randomized, controlled trial of early versus late initiation of dialysis. , 2010, The New England journal of medicine.

[18]  H. Pehamberger,et al.  Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[19]  P. Brigidi,et al.  Through Ageing, and Beyond: Gut Microbiota and Inflammatory Status in Seniors and Centenarians , 2010, PloS one.

[20]  G. Triadafilopoulos,et al.  Risk of perforation from a colonoscopy in adults: a large population-based study. , 2009, Gastrointestinal endoscopy.

[21]  N. Hunt,et al.  The role of granulocyte macrophage-colony-stimulating factor in acute intestinal inflammation , 2008, Cell Research.

[22]  J. Morley The aging gut: physiology. , 2007, Clinics in geriatric medicine.

[23]  Y. Belkaid,et al.  A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism , 2007, The Journal of experimental medicine.

[24]  J. Belaiche,et al.  Noninvasive Assessment of Crohn's Disease Intestinal Lesions with 18F-FDG PET/CT , 2007, Journal of Nuclear Medicine.

[25]  A. Feldman,et al.  Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  S. Targan,et al.  Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. , 2010, Cancer immunity.

[27]  M. Gordon Enterocolitis in Patients With Cancer After Antibody Blockade of Cytotoxic T-Lymphocyte–Associated Antigen 4 , 2008 .