In this case, diagnosis was only made after thoracic surgery was performed
October 5, 2021
In this case, diagnosis was only made after thoracic surgery was performed. wedge resection of these lesions showed defined areas of OP, which responded well to corticosteroids. Upon tapering, fresh foci of Marizomib (NPI-0052, salinosporamide A) OP developed which were resistant to Marizomib (NPI-0052, salinosporamide A) high-dose steroids and mycophenolate treatment. The TNF antagonist infliximab led to a rapid and durable regression of the inflammatory lesions. Summary This case identifies a not well-studied scenario, in which a mycophenolate-resistant PD-1 blocker-associated pneumonitis was successfully treated having a TNF neutralizing antibody. The outcome of this case suggests that infliximab might be the preferable option compared to classical immunosuppressants in the case of steroid-resistant/?dependent late onset pulmonary irAEs. Keywords: Immune checkpoint inhibitor, Malignancy immunotherapy, Pneumonitis, Lung, Immune-related adverse event Background Blocking antibodies that target the immune checkpoint PD-(L)1 have Marizomib (NPI-0052, salinosporamide A) led to durable remissions in various cancers including but not limited to melanoma, non-small cell lung malignancy (NSCLC), bladder malignancy and renal cell carcinoma [1C3]. Although PD-(L)1 targeted checkpoint inhibitors are most often well tolerated, 10C15% individuals develop severe immune-related adverse events (irAEs) [4C8]. In addition, combination immunotherapies including PD-(L)1 and CTLA-4 targeted treatments have been authorized and show an increased rate of recurrence of irAEs [9, 10]. Affections of the lung with irAEs are among the most dangerous and also most heterogenous side effects of immune checkpoint inhibitors [7, 8, 11, 12]. A recent analysis of 915 individuals showed a rate of recurrence of 5% (43 individuals) in individuals with PD-L(1) targeted monotherapy . While recommendations for the treatment of pulmonary irAEs have been developed and help to manage these side effects ([4, 6, 8]; NCCN recommendations), the use of the optimal immunosuppressant in individuals not or insufficiently responding to steroids remains less obvious. Here, we describe a case with late-onset pulmonary irAE showing as an organizing pneumonia (OP) that developed during PD-1 targeted checkpoint blockade having a corticosteroid dependency and resistance to classical immunosuppressants. We also summarize the current evidence for treatment strategies of steroid-resistant/?dependent pulmonary irAEs. Case demonstration We statement a 75-yr old man with stage IV BRAF V600E mutated malignant melanoma. On his initial 18fluoro-deoxy-glucose (FDG) positron emission tomography computed tomography?(PET-CT) scan, he presented with multiple bilateral pulmonary nodules, bone and cutaneous lesions, peritoneal metastases and a lesion at the head of the CD164 pancreas (Fig.?1a and ?andb).b). A palliative combination therapy having a BRAF- (dabrafenib 2x 150 mg) and MEK inhibitor (trametinib 2?mg) was started. Six weeks later on a CT-scan exposed a partial remission of the lung, bone and cutaneous lesions but a progression of the lesion in the pancreas. A fine needle aspiration of the pancreatic lesion confirmed metastasis of the melanoma. This metastasis was irradiated and the combination targeted therapy continued. Eight months later on, a?progression Marizomib (NPI-0052, salinosporamide A) with several new pulmonary lesions and peritoneal metastasis (Fig.?1) was observed and a second line therapy with the CTLA4 inhibitor ipilimumab (3?mg/kg) started. After 2?cycles, a disease progression (Fig.?1c) prompted a third line therapy with the PD-1 inhibitor pembrolizumab and radiotherapy of a myocardial metastasis. After the start of pembrolizumab, the condition of the patient rapidly improved and the patient achieved a good partial remission (Fig.?1). At 24?weeks under pembrolizumab a program CT-scan showed multiple bilateral part stable lung lesions in the top parts of the lung. At that stage, the patient reported NYHA II dyspnea. Endoscopically the tracheobronchial system was unremarkable. Bronchoalveolar lavage (BAL) shown only a slight lymphocytosis of 13%?lymphocytes without indications of?pulmonary infection (bad microbiological cultures and PCR for viral pathogens). A transbronchial lung biopsy showed only normal lung morphology. Since it was unclear if the new lesions were metastases, we decided to surgically obtain a histological specimen. Wedge resection of several?nodular lesions of the lung was therefore performed. Surprisingly, only one pulmonary.