Patients with immune checkpoint inhibitor (ICI)-related diarrhoea/colitis (ir-D/C) should receive a biopsy, even if they have macroscopically normal bowel, according to research led by the Royal Marsden NHS Foundation Trust.
All advanced melanoma patients treated with ICI therapy at the Royal Marsden Hospital between 2011 and 2016 were reviewed to identify cases of ir-D/C. A total of 117 any-grade ir-D/C episodes occurred in 109 (21%) patients out of a total of 519 treated - 77 cases with ipilimumab, 17 with anti-PD1 (nivolumab or pembrolizumab) and 23 with ipilimumab and nivolumab (ipi+nivo). Seven patients had ir-D/C more than once on different lines of treatment.
Median onset of all-grade ir-D/C after starting ICI therapy was 41 days for ipilimumab, 91 days for anti-PD1 and 45 days for ipi+nivo.
In 71 of 117 (61%) patients, ir-D/C episodes were treated with corticosteroid (CS); 54 were steroid-responsive and 17 were steroid-refractory and received additional anti-tumor necrosis factor (TNF) treatment.
Rates of grade 3 ir-D/C were higher than reported in clinical trials, averaging 58 days. Median overall CS duration was longer in the grade 3/4 ir-D/C steroid-refractory group (94 vs 45 days).
Infection developed in 15 per cent of CS recipients and in 35 per cent of anti-TNF recipients. About half (55%) received flexible sigmoidoscopy.
Of these patients, 38/65 (58%) had macroscopic colitis and 12/65 (18%) had microscopic colitis. The steroid-refractory group had more macroscopic changes (76%) than the steroid-responsive group (54%).
The authors said the findings demonstrate that microscopic colitis is an important subgroup. They advocate for biopsies in ir-D/C, even with macroscopically normal bowel.