Moderate Colitis Not Requiring Intravenous Steroids Is Associated with Improved Survival in Stage IV Melanoma after Anti-CTLA4 Monotherapy, But Not Combination Therapy

Abstract

Background For patients with melanoma, gastrointestinal immune-related adverse events are common after receipt of anti-CTLA4 therapy. These present difficult decision points regarding whether to discontinue therapy. Detailing the situations in which colitis might predict for improved survival and how this is affected by discontinuation or resumption of therapy can help guide clinical decision-making. Materials and Methods Patients with stage IV melanoma receiving anti-CTLA4 therapy from 2008 to 2019 were analyzed. Immune-related colitis treated with ≥50 mg prednisone or equivalent daily or secondary immunosuppression was included. Moderate colitis was defined as receipt of oral glucocorticoids only; severe colitis was defined as requiring intravenous glucocorticoids or secondary immunosuppression. The primary outcome was overall survival (OS). Results In total, 171 patients received monotherapy, and 91 received dual checkpoint therapy. In the monotherapy group, 25 patients developed colitis and a nonsignificant trend toward improved OS was observed in this group. Notably, when colitis was categorized as none, moderate or severe, OS was significantly improved for moderate colitis only. This survival difference was not present after dual checkpoint therapy. There were no differences in known prognostic variables between groups, and on multivariable analysis neither completion of all ipilimumab cycles nor resumption of immunotherapy correlated with OS, while the development of moderate colitis did significantly affect OS. Conclusion This single-institution retrospective series suggests moderate colitis correlates with improved OS for patients with stage IV melanoma treated with single-agent anti-CTLA4, but not dual agent, and that this is true regardless of whether the immune-checkpoint blockade is permanently discontinued.

Investigation of Tongxie-Yaofang formula in treating ulcerative colitis based on network pharmacology via regulating MAPK/AKT signaling pathway

“…GO biological process enrichment analysis revealed that TXYF in the treatment of UC may be related to biological processes such as endotoxin response, regulation of small molecule metabolism, regulation of reactive oxygen species metabolism, regulation of apoptosis signaling pathways, and negative regulation of cell proliferation. Excessive activation of oxidative stress (OS) can cause excessive production of free radicals, leading to lipid and protein peroxidation, which in turn leads to damage to the intestinal mucosal protective barrier and leads to the onset of UC [ 35 , 36 ]. Our molecular docking results showed that the binding energies of naringin and MAPK, as well as albiflorin and SRC, were -8.5 and -6.4 (kcal/mol), respectively, both less than -5.0, indicating strong binding activity between the drug and the target.…”

Immune checkpoint inhibitors in metastatic melanoma therapy (Review)

“…Moderate colitis which does not require the use of intravenous steroids is consistent with an improved overall survival of patients with stage IV melanoma when treated with a single anti-CTLA-4 drug, but not with combination drugs. This holds true even after the completion of therapy (159). Multiple nonrandomized studies have shown excellent results in patients who discontinue treatment after being treated for 1-2 years and disease progression is also uncommon in the following 2-5 years of treatment termination (160)(161)(162).…”