2234P - Local immune-related adverse events (irAEs) are more common in tumor-bearing organs

Background

Immune checkpoint inhibitors (ICIs) can induce dramatic anti-tumor immune responses as well as significant immune-related adverse events (irAEs). While the drivers of irAEs are poorly understood, we hypothesized that inflammation against infiltrating tumor cells could result in local inflammation or a break in immune tolerance that drive a subset of irAEs in the infiltrated organ.

Methods

The medical records of cancer patients admitted to the Massachusetts General Hospital with concern for an irAE from Feb 2011 - Nov 2021 were reviewed for radiographic evidence of metastatic or primary tumors in the liver and/or lungs and a diagnosis of irHepatitis and/or irPneumonitis during admission. Cases with radiation to the irAE organ in the prior year were excluded. Multivariable analysis using logistic regression was used to obtain the odds ratios of irAEs in tumor-bearing organs. Pathology specimens of irAE tissues were reviewed for histologic evidence of tumor cells.

Results

384 hospitalized patients were identified (irHepatitis n=41, irPneumonitis n=30) (Table 2234P). Tumor-bearing liver was associated with irHepatitis (OR 2.4, 95% CI [1.2, 4.7], p = 0.011), even after considering only biopsy-proven cases of irHepatitis (n = 34, OR 2.6, 95% CI [1.2, 5.4], p = 0.0093). Tumor-bearing lungs were also associated with irPneumonitis (OR 2.6, 95% CI [1.1-6.6], p = 0.034). Both associations remained significant after adjusting for dual ICI use. Four cases from patients with irAEs further identified histological evidence of radiographically occult metastases in organs with irAEs. T-cell receptor sequencing of irAEs in tumor-bearing organs will be used to further define immunologic features of these irAEs. Table: 2234P

Patients with tumor-bearing organs and irAEs

Conclusions

In a pan-cancer cohort, radiographic evidence of tumor infiltration in the lung or liver is a risk factor for the development of irAEs in that same organ. Tumor infiltration may increase the risk for developing an irAEs in that organ, and these cases may have distinct molecular and clinical features.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S.M. Blum: Financial Interests, Personal, Stocks or ownership: 76 Bio, Kronos Bio, Allogene Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: Two River Consulting, Third Rock Ventures. L. Zubiri: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck. D.A. Zlotoff: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Freeline Therapeutics, Intrinsic Imaging. D. Juric: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Genentech, Syros, Eisai, Vibliome, Mapkure, Relay Therapeutics, PIC Therapeutics; Financial Interests, Institutional, Research Funding: Novartis, Genentech, Syros, Eisai, Pfizer, Takeda, Ribon Therapeutics, Infinity, nventisBio 9RF, Cyteir, Blueprint, Arvinas. M. Dougan: Financial Interests, Personal, Speaker, Consultant, Advisor: ORIC Pharmaceuticals, Genentech, Sorriso Pharmaceuticals, Generate Biomedicines, Aditum, Palleon, Mallinckrodt Pharmaceuticals, Foghorn Therapeutics, Partner Therapeutics, SQZ Biotech, AzurRx, Moderna, Neoleukin Therapeutics, Veravas, Cerberus Therapeutics, Eli Lilly; Non-Financial Interests, Institutional, Research Grant: Eli Lilly. A. Villani: Financial Interests, Personal, Speaker, Consultant, Advisor: to Bristol Myers Squibb. K.L. Reynolds: Financial Interests, Personal, Advisory Board: SAGA Diagnostics; Financial Interests, Personal, Speaker, Consultant, Advisor: CME Outfitters, Medscape; Non-Financial Interests, Institutional, Research Funding: Bristol Myers Squibb. M. Mino-Kenudson: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Sanofi, Jansenn Oncology, Innate; Financial Interests, Personal, Royalties: Elsevier. R.J. Sullivan: Financial Interests, Personal, Advisory Board: Merck, Novartis, Bristol Myers Squibb, Eisai, Iovance, OncoSec, Pfizer, Replimune, Marengo; Financial Interests, Personal, Royalties: Up-To-Date; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Local PI: GSK, Sanofi, Moderna, Biomed Valley Discoveries, Astex, Compugen, Beigene, Novartis, Rubius, Alkermes, Synthekine; Financial Interests, Institutional, Coordinating PI: Pfizer, Roche-Genentech, Simcha Therapeutics, OnKure, Marengo. All other authors have declared no conflicts of interest.