P2396 - Safety and Predictors of Recurrence in Immune Checkpoint Inhibitor Rechallenge Post-Immune-Mediated Diarrhea and Colitis

Award: ACG Presidential Poster Award

Carolina Cruz, MD¹, Cristina Natha, MD², Rohan Patel, ³, Anirudha Chatterjee, MD⁴, Varun Vemulapalli, MD², Nina Quirk, MD, MS⁵, Rachel Mortan, MD⁶, Humberto R.. Nieves-Jiménez, MD⁷, Rohan Ahuja, MD⁶, Irene Lee, ⁸, Jacob Reitnauer, ⁶, Sean Ngo, BS², Jarrett Rong, MD⁹, Tanvi Gupta, MD¹⁰, Reema Patel, ¹¹, Sharada Wali, MBBS, MPH¹, Maria Julia M. N.. Santos, MD³, Krishnavathana Varatharajalu, MD³, Jessemel Estrada, ¹¹, Yinghong Wang, MD, PhD, MS¹
1University of Texas MD Anderson Cancer Center, Houston, TX; 2McGovern Medical School at UTHealth, Houston, TX; 3MD Anderson Cancer Center, Houston, TX; 4University of Texas Medical Branch, Galveston, TX; 5University of Texas Health Sciences Center in Houston, Houston, TX; 6University of Texas at Houston, Houston, TX; 7Baylor College of Medicine / MD Anderson Cancer Center, Houston, TX; 8Baylor College of Medicine, Houston, TX; 9McGovern Medical School at UTHealth Houston, Houston, TX; 10University of Texas Health, McGovern Medical School, Houston, TX; 11University of Texas Medical Branch, Houston, TX

Introduction:

Immune checkpoint inhibitors (ICIs) are associated with immune-mediated diarrhea and colitis (IMDC), often necessitating treatment interruption. While IMDC is usually manageable with immunosuppression, guidance on ICI resumption remains limited. Rechallenging patients with prior responses yields similar outcomes to non-rechallenged cases, while those without initial responses may experience improved progression-free survival upon resumption. This study evaluates recurrence rates, predictive factors, and potential timing window for ICI rechallenge following IMDC.

Methods:

This retrospective, single-center study evaluated patients with IMDC between 2015-2025. Statistical analysis included ROC, binary and Cox regression using SPSS 24.

Results: Of 1128 patients, 58.6% were male and 89.8% white. While 94 patients continued ICI during IMDC, 1026 discontinued; of these, 309 (30.1%) were later rechallenged after a median of 113 days, with recurrence in 98 (31.7%). IMDC management prior to rechallenge involved corticosteroids alone in 89 patients (CTCAE grade > 2 diarrhea and colitis in 74.1% and 43.8%, respectively, recurrence in 20.2%). Corticosteroids plus selective immunosuppressive therapy in 185 patients, with grade > 2 diarrhea in 82.7% and colitis in 46.4%; recurrence was 39.5%. Supportive care alone was given to 30 patients, with grade > 2 diarrhea and colitis in 34% and 30%, respectively, and recurrence was 16.6%. Three patients received front-line fecal microbiota transplantation, all with grade > 2 diarrhea or colitis; no recurrences occurred. ROC and Cox regression did not identify an optimal ICI-free interval to reduce recurrence. However, longer duration of initial IMDC trended toward higher recurrence (HR: 1.01 CI:1.0-1.02, p=0.072), suggesting that event severity may be predictive. On univariate analysis, prior cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor use (OR: 0.4 CI:0.2-0.8, p=0.019) and initial chronic inflammation (OR:0.3 CI:0.1-0.9, p=0.034) were protective, while hospitalization correlated with increased recurrence risk (OR:2.3 CI: 1.2-4.4, p=0.011).

Discussion:

In this larger single-center cohort, ICI rechallenge after IMDC was feasible, with recurrence in roughly 31.7% of cases. Protective factors included initial CTLA-4 use and chronic inflammation, while hospitalization and longer IMDC index event trended toward increased risk. These findings support a risk-adapted strategies for ICI reintroduction.


Figure: Table 1.

Disclosures:
Carolina Cruz indicated no relevant financial relationships.
Cristina Natha indicated no relevant financial relationships.
Rohan Patel indicated no relevant financial relationships.
Anirudha Chatterjee indicated no relevant financial relationships.
Varun Vemulapalli indicated no relevant financial relationships.
Nina Quirk indicated no relevant financial relationships.
Rachel Mortan indicated no relevant financial relationships.
Humberto Nieves-Jiménez indicated no relevant financial relationships.
Rohan Ahuja indicated no relevant financial relationships.
Irene Lee indicated no relevant financial relationships.
Jacob Reitnauer indicated no relevant financial relationships.
Sean Ngo indicated no relevant financial relationships.
Jarrett Rong indicated no relevant financial relationships.
Tanvi Gupta indicated no relevant financial relationships.
Reema Patel indicated no relevant financial relationships.
Sharada Wali indicated no relevant financial relationships.
Maria Julia Santos indicated no relevant financial relationships.
Krishnavathana Varatharajalu indicated no relevant financial relationships.
Jessemel Estrada indicated no relevant financial relationships.
Yinghong Wang indicated no relevant financial relationships.

Carolina Cruz, MD¹, Cristina Natha, MD², Rohan Patel, ³, Anirudha Chatterjee, MD⁴, Varun Vemulapalli, MD², Nina Quirk, MD, MS⁵, Rachel Mortan, MD⁶, Humberto R.. Nieves-Jiménez, MD⁷, Rohan Ahuja, MD⁶, Irene Lee, ⁸, Jacob Reitnauer, ⁶, Sean Ngo, BS², Jarrett Rong, MD⁹, Tanvi Gupta, MD¹⁰, Reema Patel, ¹¹, Sharada Wali, MBBS, MPH¹, Maria Julia M. N.. Santos, MD³, Krishnavathana Varatharajalu, MD³, Jessemel Estrada, ¹¹, Yinghong Wang, MD, PhD, MS¹. P2396 - Safety and Predictors of Recurrence in Immune Checkpoint Inhibitor Rechallenge Post-Immune-Mediated Diarrhea and Colitis, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.