Concomitant Human Herpes Virus 6 and nivolumab-related pneumonitis: Potential pathogenetic insights

Abstract

The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC); however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6) in a nivolumab treated patient with NSCLC. Potential pathogenetic mechanisms are discussed.

Immune Checkpoint Inhibitor-Associated Pneumonitis in Non-Small Cell Lung Cancer: Current Understanding in Characteristics, Diagnosis, and Management

“…Our analysis (Table 2) showed that the overall recurrence ratios with and without re-challenge ICI therapy were 6.82% (3/44) and 22.73% (10/44), respectively. Among three patients (65,73,81) who re-challenged ICI therapy after clinical regression of CIP, two experienced recurrence after restarting ICIs (65,81), and one patient successfully improved by discontinuing immunotherapy and beginning treatment with antibiotics and steroids (73). Recurrent pneumonitis severity, location of involvement, and pattern might vary compared with the initial manifestation of CIP.…”

“…The interstitial inflammatory infiltration might include elevated levels of eosinophil, poorly formed granulomas, and lymphocytes (18). The cases that we included specifically mentioned the pathological manifestation of alveolar parenchyma with fibroblast foci (four cases) (73,78,79,85), mild collagen expansion of the alveolar septa (one case) (78), nonspecific chronic inflammation (four cases) (73,78,85), and atypical cells (one case) (79).…”

Infections Simulating Immune Checkpoint Inhibitor Toxicities: Uncommon and Deceptive

“…One case of Epstein-Barr (EBV)-induced acute cerebellar ataxia (confirmed with positive EBV DNA in the blood and CSF), and a case of fatal encephalitis, possibly in combination with concomitant pembrolizumab neurotoxicity have been reported [ 13 , 14 ]. Finally, a single case of biopsy-proven human herpes virus 6 pneumonitis [ 15 ] and 2 cases of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strictly simulating ICI-induced pneumonitis have been reported [ 16–18 ].…”

Nintedanib in an elderly non-small-cell lung cancer patient with severe steroid-refractory checkpoint inhibitor-related pneumonitis: A case report and literature review

“…Activated fibroblasts and myofibroblasts can secrete ECM components, while myofibroblasts can produce contractile apparatus, such as α-smooth muscle actin microfilaments, which leads to the formation of fibroblastic foci and deposition of ECM ( 90 ). Fibroblastic foci in the alveolar parenchyma ( 91 – 93 ) and collagen expansion of the alveolar septa ( 94 ) have been detected in CIP lungs. These changes can destroy normal lung structures, causing a characteristic “honeycombing” morphology.…”