Anti-PD-1 Inhibitor-Related Pneumonitis in Non-Small Cell Lung Cancer

Abstract

The recent approval of two PD-1 inhibitors for the treatment of non-small cell lung cancer (NSCLC) has rapidly led to the widespread use of these agents in oncology practices. Pneumonitis has been recognized as a potentially life-threatening adverse event among NSCLC patients treated with PD-1 inhibitors; however, the detailed clinical and radiographic manifestations of this entity remain to be described. We report on two cases of anti-PD-1 pneumonitis in advanced NSCLC patients treated with nivolumab after its FDA approval. Both patients presented with ground-glass and reticular opacities and consolidations in a peripheral distribution on CT, demonstrating a radiographic pattern of cryptogenic organizing pneumonia. Consolidations were extensive and rapidly developed within 8 weeks of therapy in both cases. Both patients were treated with corticosteroids with subsequent improvement of respiratory symptoms and radiographic findings. One patient experienced recurrent pneumonitis after completing corticosteroid taper, or a "pneumonitis flare," in the absence of nivolumab retreatment, with subsequent improvement upon corticosteroid readministration. With the increasing use of immune checkpoint inhibitors in a growing number of tumor types, awareness of the radiographic and clinical manifestations of PD-1 inhibitor-related pneumonitis will be critical for the prompt diagnosis and management of this potentially serious adverse event.

Fig. 1. Chest CT images for Case 1

A, B. Chest CT at 8 weeks of nivolumab therapy demonstrated new GGO, reticular opacities, and consolidation in lower lobes predominantly on the left, with a peripheral and lower distribution, radiographically representing a COP pattern (arrows). C–D. On chest CT at 15 weeks of therapy, the findings significantly increased and involved all lobes, with multifocal areas of GGO, reticular opacities, and consolidation (arrows), as well as centrilobular nodularity and traction bronchiectasis in predominantly peripheral distribution. The overall features demonstrated a COP pattern, while the progressive nature was also indicative of developing ARDS. E–F. Further follow-up CT after 4 weeks of prednisone treatment showed a significant decrease of the CT findings with residual GGOs, demonstrating a “reversed halo” sign with central GGO surrounded by dense air-space consolidation of crescentic shape (F, arrows), which has been reported as a radiographic manifestation of COP. G–H. Chest CT scan 4 weeks after the completion of prednisone treatment showed a development of dense consolidations with GGOs and reticular opacities (arrows) in peripheral and multifocal distributions, involving both upper and lower lobes, again demonstrating COP pattern as noted during the first episode of PD-1 pneumonitis. Given the similarity of radiographic and clinical manifestations with the 1^st episode, the patient restarted prednisone for treatment of a “pneumonitis flare”. I–J. Follow-up chest CT taken 2 weeks after starting the 2^nd course of prednisone therapy demonstrated decrease of consolidation and GGOs (arrows), indicating improving pneumonitis in response to corticosteroid therapy.

Fig. 2. Chest CT images for Case 2

A–D. Axial (A–C) and sagittal (D) images of chest CT scan at 4 weeks of therapy demonstrated multifocal areas of GGO, reticular opacities, and extensive consolidation in the left lung with a peripheral distribution, demonstrating a COP pattern (arrows).