A Case of Immune Checkpoint Inhibitor Refractory Colitis Treated with Mycophenolate and High-dose Steroids

Abstract

Immune checkpoint inhibitors (ICPI) are a class of chemotherapy agents that have emerged as a front-line treatment option for multiple cancers. Nivolumab is an ICPI agent commonly used to treat metastatic melanoma. Although promising, the adverse reaction of this class is broad and per reports, the incidence of colitis is <6%. We present the case of a 71-year-old male with a history of metastatic melanoma who was being treated with nivolumab. The patient was two weeks into his treatment regimen when he began complaining of multiple loose, bloody stools. Because of these symptoms, his nivolumab was discontinued. However, despite discontinuation, his symptoms persisted and the patient underwent a colonoscopy. He was found to have diffuse inflammation of the colon and was diagnosed with nivolumab-induced colitis. Subsequently, the patient underwent multiple treatments, including high-dose steroids, infliximab, and vedolizumab (Entyvio), with no resolution of symptoms. After several months of failed treatment, the patient was readmitted to the hospital for refractory colitis. He was started on high-dose steroids and underwent a repeat colonoscopy, which again showed diffuse colitis. Because of the previously failed treatment options, mycophenolate, an immunosuppressant, was initiated in combination with his steroids. After three days of high-dose steroids and mycophenolate, the patient's symptoms resolved, with no subsequent apparent symptoms of colitis. We present a case of nivolumab-induced colitis, refractory to multiple immunosuppressive medications, which was successfully treated with mycophenolate and high-dose steroids.

Successful Treatment of an Immune-Mediated Colitis Induced by Checkpoint Inhibitor Therapy in a Patient with Advanced Melanoma

“…Randhawa et al [12] have recently presented the case of a 27-year-old female with severe colitis, refractory to methylprednisolone, infliximab and mycophenolate mofetil, who responded to vedolizumab, which is a humanized monoclonal antibody against α4β7 integrin [12]. On the other hand, Alcantar et al [13] presented the case of a patient in whom clinical remission was observed under steroids and mycophenolate after high-dose steroids, infliximab, and vedolizumab failed to achieve a resolution of the patients’ symptoms [13]. Nevertheless, we decided to keep our immunosuppression regime limited to steroids and infliximab because of the induction of a remarkable clinical remission, even though a daily mesalazine dose is necessary in order to preserve this effect.…”

Immune Checkpoint Inhibitor-Associated Colitis: From Mechanism to Management

“…Besides, there are also other potential biologics for refractory ICI-related colitis (203). Anti-IL-1 blockade (anakinra), anti-IL-17 blockade (ixekizumab), anti-IL-23 and anti-IL-12 blockade (ustekinumab) (209), mycophenolate mofetil (MMF) (210,211), and ciclosporin (54), aiming at blocking critical inflammatory components participating in the pathophysiological process of irAEs, are reported to exert considerable effects in treating severe CIC. Besides, Janus kinase (JAK) inhibitors (tofacitinib) have shown efficacy in CIC patients (212).…”

Checkpoint Inhibitor-Induced Colitis—A Clinical Overview of Incidence, Prognostic Implications and Extension of Current Treatment Options

“…Although there are considerably less data, a systematic review showed equal efficacy of vedolizumab in comparison to infliximab [ 93 ]. Treatment with mycophenolate mofetil has also been described [ 94 , 95 ]. In most cases, these therapies can be discontinued within a reasonable period, but reports of treatment for an indefinite period due to persistent irAE have also been described [ 96 ].…”