Royal North Shore Hospital, Sydney, Australia
Catriona Harvey , Kazi Jannatun Nahar , Serigne N. Lo , Tasnia Ahmed , Sheima Farag , Nadia Yousaf , Kate Young , Liselotte Tas , Aafke Meerveld-Eggink , Christian U. Blank , Austin Thomas , Jennifer Leigh McQuade , Bastian Schilling , Douglas Buckner Johnson , Roberto Martin Huertas , Ana Maria Arance , Joanna Lee , Lisa Zimmer , Georgina V. Long , Alexander M. Menzies
Background: Immune checkpoint inhibitor (ICI) GI tox (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab (IFx); however not all pts respond and best management of IFx-Refractory ICI GI toxicity (IRIGItox) is not clear. Methods: We conducted an international multi-centre retrospective case series. IRIGItox was defined as failure of symptom resolution ≤ Gr 1 (CTCAE v5.0) following ≥ 2 IFx doses or failure of symptom resolution ≤ Gr 2 after 1 dose. Data were extracted regarding demographics, steroid use, response and survival. Tox was graded at symptom onset and time of IFx failure. Efficacy of IFx refractory therapy was assessed by symptom resolution, time to resolution and steroid wean. Results: 78 pts were identified; med age 60 yrs (95% CI 56-65), 56% male. 70 (90%) had melanoma, 55 (71%) had advanced-stage, 60 (77%) received anti-CTLA-4 (with anti-PD1 50, single agent 10). Most had colitis (N=75, 96%) and ≥ Gr 3 tox (N=74, 95%) at symptom onset. Pre-IFx investigation varied: imaging 37%; faecal calprotectin 29%; endoscopy 59%. All pts received Med time to steroid initiation was 3 days (95% CI 2-4). 46 (59%) had primary steroid refractory disease,. Med time from symptom onset to IFx was 18 days (95% CI 12-23), a med 2 (range 1-6) doses of IFx were given, 69 (88%) pts received > 1 IFx dose. Across 78 pts, 105 post IFx treatments were given: calcineurin inhibitors (ciclosporin, tacrolimus, 32); antimetabolites (mycophenolate, azathioprine, 26); non-TNF-α MABs (vedolizumab, ustekinumab, 20); non-targeted anti-inflammatory (mesalazine, 16); non-pharmacological (colectomy 5, faecal transplant 1, photophoresis 1). 4 pts did not receive therapy for IRIGItox. Of these, 2 died of melanoma prior to resolution of tox; 1 had resolution after 4 doses IFx, 1 had recurrent melanoma and flare of tox on PD1 re-challenge. IRIGItox outcomes by post IFx treatment are shown in Table. Conclusions: This retrospective case series confirms heterogeneous management of IRIGItox. Non-pharmacological interventions and calcineurin inhibitors appear most likely to result in tox resolution. Calcineurin inhibitors have the shortest time to resolution in responders. Further details on post-IFx management and oncological outcomes will be examined.
Post IFx treatment (n) | Tox resolution n (%) | If resolved, time to resolution (med (95% CI), days) | If resolved, time to physiological steroid (med (95% CI), days) |
---|---|---|---|
All (105) | 55 (52) | 28 (16-44) | 54 (49-67) |
Calcineurin inhibitor (32) | 22 (67) | 14 (8-30) | 51 (38-74) |
Antimetabolite (26) | 12 (46) | 18 (10-68) | 54 (43-225) |
Non TNF-α MAB (20) | 8 (40) | 66 (50-217) | 126 (72-293) |
non-targeted anti-inflammatory (16) | 7 (44) | 41 (10-64) | 7 (0-64) |
non-pharmacological (7) | 5 (71) | 28 (22-369) | 53 (42-61) |
Nil (4) | 1 (25) | 55* | 55* |
*Calculated from last dose IFx
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