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. 2024 Jan 5;29(1):e118-e130.
doi: 10.1093/oncolo/oyad238.

Immune-Related Diarrhea and Colitis in Non-small Cell Lung Cancers: Impact of Multidisciplinary Management in a Real-World Setting

Laura Bonanno  1 , Martina Lorenzi  1   2 , Davide Massa  1   2 , Mattia De Nuzzo  1   2 , Valentina Angerilli  3 , Fabiana Zingone  2   4 , Brigida Barberio  2   4 , Alberto Russi  5 , Fabio Girardi  1 , Alessandra Ferro  1 , Alessandro Dal Maso  1 , Stefano Frega  1 , Giulia Pasello  1   2 , Angelo Paolo Dei Tos  3 , Marina Coppola  5 , Matteo Fassan  3   6 , Edoardo Vincenzo Savarino  2   4 , Valentina Guarneri  1   2
Affiliations

Immune-Related Diarrhea and Colitis in Non-small Cell Lung Cancers: Impact of Multidisciplinary Management in a Real-World Setting

Laura Bonanno et al. Oncologist. .

Abstract

Introduction: Immune-related adverse events (irAEs) constitute a challenge in the clinical management of solid tumors. This study aims to collect real-world data on the occurrence of immune-mediated diarrhea and colitis (IMDC) in advanced non-small cell lung cancer (aNSCLC) treated with immune checkpoint inhibitors (ICIs) and to assess the clinical impact of a multidisciplinary approach (MDA) on IMDC management.

Methods: We retrospectively collected data on patients with aNSCLC consecutively treated with ICIs, either as single agent or in combination with chemotherapy, between September 2013 and July 2022. Among patients developing IMDC, we conducted blinded revision of colonic biopsies and evaluated the clinical impact of the introduction of MDA through predefined indicators.

Results: Among the 607 patients included, 84 (13.8%) experienced IMDC. Pathological review highlighted a high prevalence of microscopic colitis (28%), with a collagenous pattern linked to longer symptoms duration (P = .01). IMDC occurred more frequently in females (P = .05) and PD-L1 expressors (P = .014) and was correlated with longer progression-free survival (17.0 vs 5.8, P < .001) and overall survival (28.3 vs 9.5, P < .001). The introduction of MDA was associated with increased employment of diagnostical tools such as fecal calprotectin test (P < .001), colonoscopy (P < .001), and gastroenterological evaluation (P = .017) and a significant decrease in both grade 3 conversion rate (P = .046) and recurrence after rechallenge (P = .016). Hospitalization rate dropped from 17.2% to 3.8% (P: ns).

Conclusion: These findings highlight the clinical relevance of IMDC and support the incorporation of a MDA to optimize the clinical management of this irAE to improve patient care. Prospective validation has been planned.

Keywords: collagenous colitis; immune checkpoint inhibitors; immune-mediated diarrhea and colitis; immune-related adverse events; immunotherapy rechallenge.

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Conflict of interest statement

Laura Bonanno declares speaker fee and participation to advisory board for AstraZeneca, Roche, MSD, Bristol-Myers Squibb, Sanofy, Novartis, outside the submitted work; is part of the steering committee for AstraZeneca; and received travel expenses from AstraZeneca and Roche. Davide Massa has received travel expenses from Eli Lilly. Giulia Pasello declares speaker fee and participation to advisory board for Amgen, AstraZeneca, BMS, Lilly, MSD, Novartis, Roche, and Janssen, and unconditioned research support from AstraZeneca and Roche. Matteo Fassan received grants from QED Therapeutics, grants and personal fees from Astellas Pharma, and personal fees from Tesaro—GSK, Diaceutics, and Roche. Edoardo Vincenzo Savarino declares speaker fees from Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; and research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, and Zeta Farmaceutici. Valentina Guarneri declares speaker fees from Eli Lilly, Exact Sciences, Novartis, Pfizer, Gilead, MSD, Amgen, Sanofi, Merck Serono, and Eisai outside the submitted work. The other authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Outcome of patients treated with ICIs according to the presence of immune-related diarrhea in terms of progression-free survival (PFS, A) and overall survival (OS, B).
Figure 2.
Figure 2.
The figure summarized the changes in management and outcome of immune-related diarrhea and colitis (IMDC) after the introduction of multidisciplinary discussion. *In conversion to G3 group were included cases experiencing worsening of symptoms during active management.
Figure 3.
Figure 3.
Representative examples of the microscopic alterations found in colic mucosa of patients treated with immune checkpoint inhibitors. (A) Crypt atrophy. (B) Apoptotic bodies within a gland. (C) Mild crypts’ distortion. (D) Lamina propria expansion and mucin depletion. (E) Collagenous band. (F). CD3 immunostaining showing moderate intraepithelial lympho-monocitic infiltrate. (G) Lympho-monocitic and plasmacellular infiltrate within the lamina propria. (H) Granulocytic infiltrate within the lamina propria associated with cryptitis. (I) Cryptic abscess. (J) Subepithelial macrophages. (K) Ischemic-like colitis features and superficial erosion. (L) Paneth metaplasia.
See this image and copyright information in PMC

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