Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Abstract

Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn’s disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.

Enterocolitis due to immune checkpoint inhibitors: a systematic review

“…A single dose of infliximab is often sufficient to improve symptoms, although a second infusion 2 weeks later may be needed in some cases 23 25 29 33 49 50. Vedolizumab, a monoclonal antibody blocking α₄β₇ integrin, was administered to six patients with steroid-dependent or steroid-refractory enterocolitis due to ipilimumab 51. Time to steroid-free remission was 56 days, which is comparable to the time to spontaneous remission.…”

“…Some patients with steroid-refractory colitis improved with infliximab, but data are scarce 59 63 72. Patients with anti-PD-1-induced GI IrAE have received mesalazine, vedolizumab,51 tocilizumab and adalimumab-methotrexate combination with reported improvement 73–75. One patient who had skin and GI irAE induced by pembrolizumab improved with secukinumab but subsequently lost antitumour efficacy 76…”

Colitis after checkpoint blockade: A retrospective cohort study of melanoma patients requiring admission for symptom control

“…There are two primary patterns of colitis reported: similar significant ulcerations or normal mucosa with microscopic damage . Management of CPI‐related GEC relies on high‐dose corticosteroids with escalation to infliximab, though alternative second‐line therapies are emerging . The particular steroid administered does not seem to impact clinical course .…”

Management of Gastrointestinal Toxicity from Immune Checkpoint Inhibitor

“…Some case reports suggest that vedolizumab may be an effective drug in steroid-refractory or steroid-dependent patients [24, 25]. A recent study with seven patients with mild to moderate, steroid-dependent or steroid-refractory ipilimumab-induced enterocolitis has revealed that six out of seven patients treated with vedolizumab achieve remission and no adverse events were reported [26]. Neither corticosteroids nor infliximab appear to influence response and survival of patients treated with ICPIs [1].…”