Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study.

Abstract

OBJECTIVES:

Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP.

MATERIALS AND METHODS:

We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed.

RESULTS:

Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3-4 CIP. All 12 patients with grade 3-4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy.

CONCLUSIONS:

The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

• Authors: X Lin, T Lu, S Li, X Xie, X Chen, J Jiang, Y Qin, Z Xie, M Liu, M Ouyang, N Zhong, Y Song, C Zhou
• Journal: Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 23 Issue 2 Pg. 389-396 (Feb 2021) ISSN: 1699-3055 [Electronic] Italy
• PMID: 32613413 (Publication Type: Journal Article)

Chemical References

• Antibodies, Viral
• Antiviral Agents
• Glucocorticoids
• Immune Checkpoint Inhibitors
• Immunoglobulin G
• Viral Matrix Proteins
• cytomegalovirus matrix protein 65kDa

Topics

• Aged
• Antibodies, Viral (blood)
• Antiviral Agents (therapeutic use)
• Cytomegalovirus (immunology)
• Cytomegalovirus Infections (complications, drug therapy)
• Female
• Glucocorticoids (therapeutic use)
• Humans
• Immune Checkpoint Inhibitors (adverse effects)
• Immunoglobulin G (blood)
• Lung Neoplasms (drug therapy, virology)
• Male
• Middle Aged
• Pneumonia (chemically induced, drug therapy, immunology, pathology)
• Retrospective Studies
• Viral Matrix Proteins (blood)
• Virus Activation