Practice Changes in Management of Gastrointestinal Immune-Related Adverse Events at a Tertiary Care Cancer Center

Introduction: Immunotherapy can give rise to systemic immune-related adverse events (irAEs) that are an obstacle to effective cancer treatment. Our understanding of this disease has evolved rapidly with extensive research over the years, and management guidelines are constantly updated. We aim to explore how management of gastrointestinal (GI) irAEs at a tertiary cancer care center has changed to identify areas for potential improvement. Methods: This was a single-center, retrospective chart review of all patients with immune-mediated diarrhea and colitis (IMDC) from July to September of 2019 and 2021. The follow-up window was for up to a year after diagnosis. We collected data on patient demographics, clinical management, and disease course and outcomes. Results: 77 patients were included in this study. We found worsening rates of GI specialty consultation (94.9% in 2019 vs 86.8% in 2021), hospitalization (64.1% vs 71.7%), follow-up after discharge (92.0% vs 48.2%, P=0.007), endoscopic evaluation at baseline (94.8% vs 60.5%, P< 0.001) and follow-up (38.9% vs 27.2%), and selective immunosuppressive therapy (SIT) use (74.3% vs 42.1%, P=0.004). Despite this, there was a marked improvement in outcomes including symptom duration (median 43.5 days in 2019 vs 24.5 in 2021, P=0.036), need for >1 steroid tapering courses (38.5% vs 18.5%, P=0.06), hospital readmission rates (53.1% vs 33.3%), and colitis recurrence (36.1% vs 28.0%) and remission rates (92.3% vs 97.1%). This was true across different diarrhea and colitis CTCAE grades. The pooled data suggests that GI consultation prior to an event is significantly associated with lower readmission (P=0.000) and recurrence (P=0.001) rates, with earlier time to consultation also playing a role (P< 0.05). Finally, SIT use is also associated with less recurrence (OR: 0.3, P=0.012) (Table 1). Conclusion: This is one of the few qualitative studies exploring current practice in managing GI irAEs. Changes in practice between 2019 and 2021 likely reflect a variety of factors including an evolving knowledge of this disease as well as the impact of the COVID-19 pandemic. While overall disease outcomes are better in more recent years, there is room for improvement. Ensuring adequate and timely GI consultation and endoscopic evaluation rates, and more SIT use could help reduce hospital readmission and disease recurrence. Together, these findings can help improve the quality of GI irAE management algorithms at our institution. Table 1. - a. Differences in GI irAE Clinical Management and Disease Outcomes Across 2019 and 2021 No. of new colitis cases (%) P-value Outcome 2019, N=39 2021, N=38 Symptom duration, days, median (IQR) 43.5 (18.8-90.8) 24.5 (12.5-46.5) 0.036* Outpatient GI consult before hospitalization1 23 (82.1%) 16 (72.7%) 0.502 Any GI consultation2 37 (94.9%) 33 (86.8%) 0.262 Outpatient irAE treatment before hospitalization1 24 (88.9%) 16 (72.7%) 0.266 Time to GI consultation, days, median (IQR) 21 (12-41.5) 16 (5.5-41.5) 0.365 Hospitalization 25 (64.1%) 27 (71.1%) 0.515 Length of hospital stay, days, median (IQR) 5 (3-8.75) 7 (3-8) 0.495 Inpatient consult 22 (91.7%) 21 (80.8%) 0.267 GI follow-up after discharge 23 (92.0%) 13 (48.2%) 0.007* Time to GI follow-up, days, median (IQR) 20 (7.8-58.8) 31 (14-57) 0.451 Endoscopic evaluation 37 (94.8%) 23 (60.5%) < 0.001* Time from irAE to endoscopy, days, median (IQR) 7 (2-12.3) 8 (2-34.3) 0.468 Follow-up scope 14(38.9%) 6(27.2%) 0.408 Symptom improvement 28 (71.8%) 28 (80%) 0.411 Duration of steroid use, days, median (IQR) 35(28-88) 39.5 (27.8-66.8) 0.880 Need for >1 steroid tapering course 15 (38.5%) 7 (18.5%) 0.06 Need for >2 steroid tapering courses 6 (15.4%) 0 (0%) 0.014* SIT use3 29 (74.3%) 16 (42.1%) 0.004* Colitis response/remission at final follow-up4 36 (92.3%) 34 (97.1%) 0.272 Hospital readmission 5 (21.7%) 7 (28.0%) 0.743 Recurrence 13 (36.1%) 9 (28.1%) 0.605 All-cause mortality 14(35.9%) 9(24.3%) 0.323 b. Chi-square analysis for associations with disease outcomes GI consultation before eventNr=59 NHr=45 GI consultation after eventNr=7 NHr=12 P-value Recurrence, n=25 18(30.5%) 7(100%) 0.001* Hospital readmission, n=12 7(13.5%) 5(100%) < 0.001* c. Chi-square analysis for associations with disease outcomes Recurrence Characteristic (outcome) Odds ratio (Confidence interval) P-value Contact with GI early vs late in colitis disease course5 (recurrence) 0.4 (0.1-0.9) 0.047* Outpatient treatment (yes vs no) 0.2 (0.1-0.6) 0.005* SIT use 0.3 (0.1-0.8) 0.012* Hospital readmission Contact with GI early vs late in colitis disease course5 (readmission) 0.2(0.04-0.7) 0.012* Abbreviations: GI = gastrointestinal; irAE, immune-related adverse event; IQR, interquartile range; SIT, selective immunosuppressive therapy; Nr, # of patients with recurrence; NHr, # of patients with hospital readmission Total IMDC cases within the 3 months study window: 2019=79; 2021=161*Statistically significant when P<0.05. 1.50 patients presented with colitis prior to hospitalization (28 in 2019 and 22 in 2021). The remaining all presented either at the ER/hospital.2Includes as an outpatient before hospitalization, as an inpatient, or as outpatient after hospital discharge.3Selective immunosuppressive therapy includes infliximab, vedolizumab, or ustekinumab.4Defined as symptom improvement to CTCAE grade 1 or 0. 5.Early GI consult: Before initiation of steroids up to 2 weeks after initiation; late GI consult: 2 or more weeks after initiation date of steroid.