The combination of nivolumab and ipilimumab results in longer progression-free survival and higher rates of response compared with ipilimumab (and numerically to nivolumab), leading to FDA approval and increased use of combination therapy with ipilimumab and nivolumab ( 5, 6). The mAbs to PD-1, pembrolizumab and nivolumab, have also shown survival benefit in phase III studies in metastatic melanoma ( 1). In metastatic melanoma, an mAb to CTLA-4 (ipilimumab) was the first drug that demonstrated improved overall survival in a randomized study, and it has also shown durable objective responses ( 2–4). CTLA-4 and PD-1/PD-L1 are negative regulators of T cell–mediated immune responses, and their blockade leads to an increase in T-cell activation and infiltration of tumors. Immune checkpoint blockade, using mAbs to cytotoxic lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1) receptors have emerged as effective treatment strategies in solid and hematologic malignancies ( 1). 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. 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). 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). Of the patients with diarrhea, 48 (48%) underwent colonoscopy and 46 (46%) underwent both CT and colonoscopy. Ninety nine (33%) of 303 patients developed diarrhea during therapy, and 46 patients (15%) received corticosteroids for colitis. 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. With the anticipated widespread use of these reagents, the timely and accurate diagnosis of immune-related colitis becomes increasingly important. Colitis can be a life-threatening toxicity for patients treated with immune checkpoint blockade antibodies.
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