113P - A multidisciplinary management of immune-checkpoint inhibitor (ICI)-related pneumonitis to improve its clinical management

Background

Treatment with ICI can associate with a wide spectrum of immune-related adverse events (irAEs). Among irAEs is immune-mediated pneumonitis (im-PN), a rare but potentially life-threatening side effect; thus, prompt diagnosis and effective management of im-PN is essential to avoid severe complications.

Methods

We collected a case series of skin cancer (melanoma-MM, squamous cell carcinoma-SCC), lung cancer (LC) and mesothelioma (MESO) patients (pts), treated with ICI at the Center for Immuno-Oncology of the University Hospital of Siena, Italy, diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN were graded using CTCAE v. 5.0.

Results

From Jan 2014 to Feb 2023, 1004 pts with MM (n=522), SCC (n=42), LC (n=342) or MESO (n=98) were treated with ICI (619 anti-PD-1, 385 combinations). Among treated pts 24 (2%) developed an im-PN, and 14 (58%) were symptomatic. Im-PN was classified grade (G)1 (10 pts), G2 (13 pts), and G5 (1 patient). Steroid treatment was promptly activated leading to complete resolution of im-PN in 22 pts. Thirteen pts resumed ICI therapy once fully-recovered from im-PN, and 2 of them experienced im-PN recurrence that completely resolved with steroids re-treatment. According to the Fleischner Society classification of drug-related pneumonitis, 3 main radiologic patterns were identified: organizational pneumonia (OP)-like (16,6%), pulmonary eosinophilia (PEo) (7,3%), and hypersensitivity pneumonitis (HP) (1,4%). Furthermore, BAL samples analysis performed in 8 (33%) symptomatic pts showed an inflammatory lymphocytic infiltrate, predominantly consisting in a foam cell-like macrophages infiltrate in 6 cases. Notably, Transmission Electron Microscopy evaluation performed in 2 of these pts, revealed multilamellar bodies, lysosomes, and lipid vacuoles into the alveolar macrophages, a scenario suggestives for a drug-mediated toxicity.

Conclusions

Im-PN associated with ICI therapy was found to be a rare and challenging side effect, with variable time onset, and heterogenous clinical presentation. A multidisciplinary characterization of im-PN helps optimizing its clinical management to resume ICI therapy.

Legal entity responsible for the study

Anna Maria Di Giacomo.

Funding

Has not received any funding.

Disclosure

M. Valente: Financial Interests, Personal, Advisory Board: Novartis. M. Maio: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Incyte, AstraZeneca, Amgen, Pierre Fabre, Eli Lilly, GSK, Sciclone, Sanofi, Alfasigma, Merck Serono; Financial Interests, Personal, Ownership Interest: Theravance, Epigen Therapeutics Srl. L. Calabro: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme; Financial Interests, Personal, Other, Educational Activities: Bristol Myers Squibb, Sanofi, AstraZeneca. A.M. Di Giacomo: Financial Interests, Personal, Advisory Board: Incyte, Pierre Fabre, GSK, Bristol Myers Squibb, Merck Sharp Dohme, Sanofi; Financial Interests, Personal, Other, Educational activities: Bristol Myers Squibb, Merck Sharp Dohme, Pierre Fabre, Sanofi. All other authors have declared no conflicts of interest.