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 ... show 1 more
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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.
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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.