Switch to Infliximab Warranted to Ease Ipilimumab-Related Diarrhoea in Advanced Melanoma

Infliximab safely and effectively eases ipilimumab-induced diarrhoea in patients with advanced melanoma, according to findings from a retrospective study presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO).

Immunosuppressants can be used to dampen immune-related toxicities caused by monoclonal antibodies, including ipilimumab, and an early switch can help minimise toxicity, noted lead investigator Edurne Arriola, MD, PhD, University Hospital Southampton, Southampton, United Kingdom, speaking here at a poster session on June 1.

Whether this strategy curtails anti-tumour killing and/or worsened disease outcome, however, has been unclear until now.

Dr. Arriola and colleagues explored the use of inflixumab for the relief of diarrhoea caused by ipilimumab 3 mg/kg in patients with metastatic melanoma. The examined the records of 90 patients (median age 64 years; range: 19 to 81 years; 51% male) for responses during and following use of inflixumab.

The primary melanoma was most commonly cutaneous (n = 69, 77%), stage M1c (n = 65, 72%), and BRAF wild type (n = 48, 54%). In the 77% of tumours for which BRAF data were available, 32% cases harboured a V600E mutation. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 52 (58%) patients and ?1 in 37 (42%) patients.

Ipilimumab was administered as second-line treatment. The majority (60%) of patients completed 4 cycles.

Twenty seven (30%) patients developed ipilimumab-related diarrhoea of any grade. Of these, 21 (80%) required oral steroids for management, which, in 12 cases, escalated to intravenous administration of methylprednisolone (1 to 2 mg/kg/24 hours). In 7 of the patients (25%), infliximab was administered for the control of grade 3/4 colitis. All patients were followed for a median of 8 months.

Patients with M1c disease, poor ECOG performance status at the time treatment began, and disease progression at week 12 had shorter survival (all P < .05). The overall survival of the patients with diarrhoea was significantly longer than that of patients without diarrhoea (8.8 versus 5.4 months; P = .041). Of those with diarrhoea, the median overall survival of 8.8 months in those treated with infliximab was more protracted compared with the 6.8 months in those who did not receive infliximab. The difference was not significant (P = .16).

"In our series, infliximab does not negatively affect the outcome of patients with advanced melanoma treated with ipilimumab, and an early switch to spare steroid toxicity appears warranted and safe," Dr. Arriola and colleagues noted.

These findings will need to be confirmed in prospective, randomised studies; however, the present findings offer encouragement that the quality of life of patients with advanced melanoma undergoing treatment can be enhanced.

Infliximab is a monoclonal antibody directed against tumour necrosis factor-alpha. It is active in the treatment of autoimmune diseases. The antibody cannot be given orally.