Mixed Infectious–Immune Pneumonitis Associated with PD-L1 Blockade - A Case of Durvalumab-Induced Lung Injury Complicated by Human Metapneumovirus Infection

Sep 30, 2026

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Durvalumab, a PD-L1 inhibitor used after chemoradiation in unresectable stage III non–small cell lung cancer, can trigger immune-mediated pneumonitis that is difficult to distinguish from infection. A 67-year-old woman developed progressive dyspnea and extensive bilateral ground-glass opacities after chemotherapy, radiotherapy, and durvalumab. Broad antimicrobial therapy failed and high-flow oxygen was needed; sputum multiplex testing identified human metapneumovirus with negative bacterial studies. High-dose methylprednisolone followed by taper produced clinical and radiologic resolution after permanent durvalumab discontinuation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

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Abstract

1. Introduction

2. Case Presentation

Case Report Mixed Infectious–Immune Pneumonitis Associated with PD-L1 Blockade: A Case of Durvalumab-Induced Lung Injury Complicated by Human Metapneumovirus Infection Luca Pipitò 1,2, *, Chiara Vincenza Mazzola 1,2, Ilenia Giacchino 1,3, Riccardo De Rosa 1, Carola Maria Gagliardo 1, Alessio Giuseppe Lipari 1, Paola Monte 1, Federica Furia 1, Erika Mannino 1,3, Rosaria Pecoraro 4, Nicola Scichilone 1 and Antonio Cascio 1,2, * Academic Editors: Sukhwinder Singh Sohal and Robert Flisiak Received: 14 November 2025 Revised: 27 November 2025 Accepted: 25 December 2025 Published: 29 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy; chiaravincenza.mazzola@community.unipa.it (C.V.M.); [ilenia.giacchino@unipa.it](ilenia.giacchino@unipa.it) (I.G.); riccardo.derosa@community.unipa.it (R.D.R.); [carolamaria.gagliardo@you.unipa.it](carolamaria.gagliardo@you.unipa.it) (C.M.G.); [alessiogiuseppe.lipari@you.unipa.it](alessiogiuseppe.lipari@you.unipa.it) (A.G.L.); [paola.monte@you.unipa.it](paola.monte@you.unipa.it) (P.M.); [federica.furia@you.unipa.it](federica.furia@you.unipa.it) (F.F.); [manninoerika@gmail.com](manninoerika@gmail.com) (E.M.) 2 Infectious and Tropical Disease Unit, AOU Policlinico “P. Giaccone”, 90127 Palermo, Italy 3 Microbiology and Virology Unit, AOU Policlinico “P. Giaccone”, 90127 Palermo, Italy 4 U.O.C di Medicina Interna con Stroke Care, AOU Policlinico “P. Giaccone”, 90127 Palermo, Italy; [rosaria.pecoraro@policlinico.pa.it](rosaria.pecoraro@policlinico.pa.it) * Correspondence: luca.pipito@community.unipa.it (L.P.); antonio.cascio03@unipa.it (A.C.) Abstract Background: Durvalumab, a PD-L1 inhibitor used as consolidation therapy after chemoradiation in unresectable stage III non–small cell lung cancer (NSCLC), can induce immunerelated adverse events, among which immune-mediated pneumonitis represents oneof the most severe. Differentiating checkpoint inhibitor pneumonitis (CIP) from infectious pneumonia is challenging due to overlapping clinical and radiologic findings. Case presentation: We describe a 67-year-old woman with stage III lung adenocarcinoma treated with chemotherapy, radiotherapy, and durvalumab, who presented with progressive dyspnea and extensive bilateral ground-glass opacities on CT imaging. Laboratory tests revealed leukopenia and elevated inflammatory markers. Despite broad-spectrum antibiotic and antiviral therapy, her condition worsened, requiring high-flow nasal cannula oxygen therapy. Multiplex molecular testing on sputum identified human metapneumovirus (HMPV), while blood cultures and urinary antigens for Streptococcus pneumoniae and Legionella pneumophila were negative. A pulmonology consultation raised suspicion for severe durvalumab-induced pneumonitis exacerbated by viral infection. High-dose methylprednisolone (2 mg/kg/day) followed by a four-week taper led to gradual clinical and radiologic resolution. Durvalumab was permanently discontinued. Discussion: To our knowledge, this is the first reported case of HMPV-associated pneumonitis in a patient receiving durvalumab. This case highlights the potential synergistic interplay between viral infection and immune checkpoint blockade, resulting in severe lung injury. Comprehensive microbiologic evaluation, including molecular diagnostics, is essential to guide therapy and distinguish infectious from immune-mediated causes. Conclusions: Early recognition of mixed infectious and immune-mediated pneumonitis, and timely corticosteroid therapy are critical to achieving favorable outcomes and preventing irreversible pulmonary damage. Keywords: durvalumab; PD-L1 inhibitor; immune checkpoint inhibitor pneumonitis

FAQs

Why is immune checkpoint inhibitor pneumonitis hard to diagnose in this setting?

Checkpoint inhibitor pneumonitis and infectious pneumonia can show overlapping clinical symptoms and radiologic findings, making differentiation challenging without integrated assessment.

What pathogen was identified in the case and how were bacterial causes assessed?

Multiplex molecular testing on sputum identified human metapneumovirus, while blood cultures and urinary antigens for Streptococcus pneumoniae and Legionella pneumophila were negative.

What treatment led to improvement and what happened to durvalumab?

High-dose methylprednisolone (2 mg/kg/day) followed by a four-week taper resulted in gradual clinical and radiologic resolution. Durvalumab was permanently discontinued.

Sep 30, 2026

Uploaded by Grenda