PTU-005 Infliximab use in immune-related diarrhoea/colitis (IRD/C)

Introduction Immune checkpoint inhibitors (ICIs) such as ipilimumab (ipi), nivolumab (nivo) and pembrolizumab (pembro) and the combination of ipi +nivo have improved response rates and survival in patients (pts) with advanced melanoma. Nivo was recently approved by the FDA as an adjuvant therapy. Responses may be durable, however associated immune-related adverse events may result in significant morbidity. Current treatment algorithms suggest that pts treated with ICIs who develop corticosteroid (CS)-refractory (CSrefr) irD/C are prescribed anti-TNF alpha antibodies such as infliximab (IFX). Little is known about the clinical features and outcomes of pts who receive IFX. Methods Pts with advanced melanoma from the Royal Marsden NHS Foundation Trust who received CS and IFX were identified from an ethically approved irD/C database (pts treated with ICIs from 2011–2016) and their medical records were reviewed, including flexible sigmoidoscopy (FS) results. Descriptive statistics and percentages were used to summarise the features of the CSrefr versus CS-responsive (CSresp) groups. Results Rates of all-grade irD/C by course of treatment were as follows: ipi 77/285 (27%), nivo or pembro 17/166 (10%), ipi +nivo 23/68 (34%). CS were prescribed in 72 (62%). 17 (15%) received IFX; 9 received 2 doses and 3 received 3 doses. 76% responded to IFX within a week; median time to improvement was 4 days (range 1–28). Table 1 outlines clinical information for the CSrefr and CSresp groups. Infection occurred in 10 episodes of IFX prescription (59%), 9 requiring antibiotics, including 2 cases of Pneumocystic jirovecii pneumonia. Conclusions 35% of irD/C due to ipi +nivo is CS-refractory. In the CSrefr group, CS duration was longer, macroscopic colitis was more common and most pts developed an infection. Interestingly time to progression of disease was longer in the CSrefr group. Prospective clinical trials are warranted to evaluate whether early IFX may reduce the burden of CS in the management of irD/C without compromising disease control.Abstract PTU-005 Table 1 CS-refractory versus CS-responsive patients CSrefr (n= 17) CSresp (n= 54) N (range) % N (range) % Ipi 8 47 30 56 Nivo/pembro 1 6 9 16 Ipi+nivo 8 47 11 20 Days from start ICI to onset of irD/C 41 - 45 - Grade 1/2 1 6 14 26 Grade 3/4 16 94 40 74 Median days from start of D/C to CS (range) 5 - 5 - Days from start CS to IFX 14(1–100) - NA - Median duration CS - - Grade 1/2 160(160–160) - 49(6–295) - Grade 3/4 79(28–279) - 47(6–204) - Extra treatment 1(vedolizumab) 6 0 0 Macroscopic abnormality on FS 13/17 76 22/41 54 Microscopic abnormality only on FS 1/17 6 9/41 22 Normal FS 2/17 12 7/41 17 Unknown FS result 1/17 6 3/41 7 Disease progression 12 67 42 79 Median days to progressive disease 170 - 101 - NB: 1 patient who had CS but unknown status re IFX is not included