ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors)

Abstract

Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.

Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections

“… For patients with irAEs who require immunosuppressive therapy such as corticosteroids and/or TNF‐α targeted agents, close monitoring should be maintained to detect early signs of infection. A multidisciplinary approach involving oncologists and infectious disease specialists is highly recommended For HBV/HCV carriers with irAEs receiving TNF‐α targeted agents, close monitoring is needed during and for several months after therapy …”

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab

“…PD-1 is a transmembrane receptor expressed on dendritic, NK, CD4, CD8, and T-cells and involved in downregulation of the immune system by promotion of activated T-cell apoptosis and diminution of regulatory T-cell apoptosis to stop unrestrained cytotoxic functions ( 3 , 4 ). Blockade of pathways involving PD-1 and its ligand is a promising treatment for cancers (melanoma, nonsmall cell lung cancer, metastatic renal cell carcinoma, head and neck carcinomas, Hodgkin lymphoma, and urothelial carcinoma) ( 4 ), although the role of PD1/programmed death ligand 1 in immune suppression and the mechanism of action of antibodies remain to be better defined.…”

“…Blockade of pathways involving PD-1 and its ligand is a promising treatment for cancers (melanoma, nonsmall cell lung cancer, metastatic renal cell carcinoma, head and neck carcinomas, Hodgkin lymphoma, and urothelial carcinoma) ( 4 ), although the role of PD1/programmed death ligand 1 in immune suppression and the mechanism of action of antibodies remain to be better defined.…”

“…Therefore, we excluded a diagnosis of neurologic IRAEs for this patient. Infections related to treatment with checkpoint inhibitors are infrequent ( 4 ). …”

“…Another reported mechanism of development of infections with use of checkpoint inhibitors is restoration of T-cell function that mimics immune restoration syndrome (IRIS), which can cause reactivation of latent tuberculosis ( 4 ) and acute progression of aspergillosis. IRIS has been reported in patients with PML, but for our patient, use of steroids and onset of PML long after treatment with nivolumab was started did not support a diagnosis of IRIS.…”