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Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management

Nishino, Mizuki
Kusumoto, Masahiko
Bankier, Alexander A
Kurihara, Yasuyuki
Zhang, Lin
Rasheed, Zeshaan
Meinhardt, Gerold
Arunachalam, Meena
Taitt, Corina
Wang, Qiang
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Journal Article
Publication Date
2023-12-07
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Abstract

Purpose: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate approved for the treatment of several advanced cancers; however, severe or fatal interstitial lung disease/pneumonitis can occur. We characterized the computed tomography (CT) patterns of T-DXd‒related pneumonitis as a marker for its clinical severity.

Materials and methods: Ninety patients with advanced cancers who developed T-DXd‒related pneumonitis in two completed single-arm clinical trials were included. Three radiologists independently characterized the CT patterns of pneumonitis at diagnosis, for analyses of those patterns' relationships with clinical severity and pneumonitis outcome.

Results: T-DXd‒related pneumonitis most commonly presented with cryptogenic organizing pneumonia (COP) pattern, observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%). A subset of cases with COP pattern demonstrated an atypical distribution with upper and peripheral lung involvement (6/65; 9%). CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others (P < .0001). Fatal pneumonitis was more common in the AIP/ARDS pattern than in others (P = .005). The onset of pneumonitis was earlier in the AIP/ARDS pattern compared with others (median time to onset: at 17.9 v 32.7 weeks of therapy; P = .019). Pneumonitis was treated by withholding T-DXd with or without corticosteroids in most patients (78/90; 87%).

Conclusion: T-DXd‒related pneumonitis most commonly demonstrated a COP pattern, with a subset having an atypical distribution. The AIP/ARDS pattern was indicative of severe, potentially fatal pneumonitis, and requires immediate clinical attention to mitigate serious adverse events.

Source

Nishino M, Kusumoto M, Bankier AA, Kurihara Y, Zhang L, Rasheed Z, Meinhardt G, Arunachalam M, Taitt C, Wang Q, Powell CA. Trastuzumab Deruxtecan‒Related Interstitial Lung Disease/Pneumonitis: Computed Tomography Imaging Patterns to Guide Diagnosis and Management. JCO Precis Oncol. 2023 Sep;7:e2300391. doi: 10.1200/PO.23.00391. PMID: 38061008.

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10.1200/PO.23.00391
PubMed ID
38061008
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