Severe colitis in patients with melanoma treated with BRAF/MEK inhibitors

Abstract

Summary Background and Aims Dual blockade of BRAF and MEK kinases is a standard of care for metastatic V600E/K BRAF mutant melanoma. This study reports the first systematic description of colitis due to BRAF and MEK inhibitors. Methods We studied consecutive patients with melanoma, treated with BRAF and MEK inhibitors, who had colitis requiring hospitalisation. Electronic files were studied; endoscopic biopsies and colectomy specimens were read centrally. Results Between January 2021 and March 2022, nine women and one man, aged 50–90 years, were studied. Nine patients received encorafenib and binimetinib; one patient received dabrafenib and trametinib. The main symptoms were diarrhoea, haematochezia, abdominal pain and intestinal obstruction. Blood tests showed anaemia, increased CRP and low serum albumin levels in most patients. All patients had ulcerations of the right colon with (2/10) or without (8/10) stenosis of the ileocecal valve, and 4/10 patients also had ulcerations distal to the right colon. Histopathological findings were suggestive of ischaemia and mild inflammation. Nine of the 10 patients discontinued BRAF/MEK inhibitors. Drugs were reintroduced in four patients, three of whom had a severe relapse of diarrhoea. Two patients required surgery and underwent intestinal resection. One patient died of enterocolitis. Conclusion BRAF/MEK inhibitors can induce severe colitis characterised by ulcerations of the right colon.

Severe Colitis in 2 Patients with Melanoma Treated with BRAF/MEK Inhibitors: Case Report and Literature Review

“…Carbonnel et al [10] reported the largest series of 10 patients with advanced melanoma who had severe BRAF/MEKi-related colitis requiring hospitalization. Nine patients were treated with encorafenib and binimetinib and 1 patient with dabrafenib and trametinib.…”

Editorial: severe colitis induced by targeted therapies in dermato‐oncology beyond check point‐inhibitors

“…Carbonnel et al have reported a series of 10 consecutive patients hospitalised in their centre for severe colitis related to treatment with a combination of BRAF and MEK inhibitors for metastatic melanoma 6 . Nine received encorafenib plus binimetinib.…”

“…4,5 Carbonnel et al have reported a series of 10 consecutive patients hospitalised in their centre for severe colitis related to treatment with a combination of BRAF and MEK inhibitors for metastatic melanoma. 6 Nine received encorafenib plus binimetinib. Symptoms included diarrhoea, hematochezia and abdominal pain; all had ulcerations in the right colon with or without ileocaecal valve stenosis or lesions elsewhere in the colon.…”