ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Intracellular signaling pathways: tyrosine kinase and mTOR inhibitors).

Abstract

BACKGROUND:

The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biologic therapies.

AIMS:

To review, from an infectious diseases perspective, the safety profile of therapies targeting different intracellular signaling pathways and to suggest preventive recommendations.

SOURCES:

Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.

CONTENT:

Although BCR-ABL tyrosine kinase inhibitors modestly increase the overall risk of infection, dasatinib has been associated with cytomegalovirus and hepatitis B virus reactivation. BRAF/MEK kinase inhibitors do not significantly affect infection susceptibility. The effect of Bruton tyrosine kinase inhibitors (ibrutinib) among patients with B-cell malignancies is difficult to distinguish from that of previous immunosuppression. However, cases of Pneumocystis jirovecii pneumonia (PCP), invasive fungal infection and progressive multifocal leukoencephalopathy have been occasionally reported. Because phosphatidylinositol-3-kinase inhibitors (idelalisib) may predispose to opportunistic infections, anti-Pneumocystis prophylaxis and prevention strategies for cytomegalovirus are recommended. No increased rates of infection have been observed with venetoclax (antiapoptotic protein Bcl-2 inhibitor). Therapy with Janus kinase inhibitors markedly increases the incidence of infection. Pretreatment screening for chronic hepatitis B virus and latent tuberculosis infection must be performed, and anti-Pneumocystis prophylaxis should be considered for patients with additional risk factors. Cancer patients receiving mTOR inhibitors face an increased incidence of overall infection, especially those with additional risk factors (prior therapies or delayed wound healing).

IMPLICATIONS:

Specific preventive approaches are warranted in view of the increased risk of infection associated with some of the reviewed agents.

• Authors: M Reinwald, J T Silva, N J Mueller, J Fortún, C Garzoni, J W de Fijter, M Fernández-Ruiz, P Grossi, J M Aguado
• Journal: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases (Clin Microbiol Infect) Vol. 24 Suppl 2 Pg. S53-S70 (Jun 2018) ISSN: 1469-0691 [Electronic] England
• PMID: 29454849 (Publication Type: Consensus Development Conference, Journal Article, Review)
• Copyright: Copyright © 2018. Published by Elsevier Ltd.

Chemical References

• Janus Kinase Inhibitors
• Protein Kinase Inhibitors
• MTOR protein, human
• Protein-Tyrosine Kinases
• TOR Serine-Threonine Kinases

Topics

• Biological Therapy (adverse effects, methods)
• Clinical Trials as Topic
• Communicable Diseases (therapy)
• Humans
• Immunocompromised Host
• Janus Kinase Inhibitors (adverse effects, therapeutic use)
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)