Risk of infection associated with targeted therapies for solid organ and hematological malignancies

Abstract

Higher risks of infection are associated with some targeted drugs used to treat solid organ and hematological malignancies, and an individual patient’s risk of infection is strongly influenced by underlying diseases and concomitant or prior treatments. This review focuses on risk levels and specific suggestions for management, analyzing groups of agents associated with a significant effect on the risk of infection. Due to limited clinical experience and ongoing advances in these therapies, recommendations may be revised in the near future. Bruton tyrosine kinase (BTK) inhibitors are associated with a higher rate of infections, including invasive fungal infection, especially in the first months of treatment and in patients with advanced, pretreated disease. Phosphatidylinositol 3-kinase (PI3K) inhibitors are associated with an increased risk of Pneumocystis pneumonia and cytomegalovirus (CMV) reactivation. Venetoclax is associated with cytopenias, respiratory infections, and fever and neutropenia. Janus kinase (JAK) inhibitors may predispose patients to opportunistic and fungal infections; need for prophylaxis should be assessed on an individual basis. Mammalian target of rapamycin (mTOR) inhibitors have been linked to a higher risk of general and opportunistic infections. Breakpoint cluster region-Abelson (BCR-ABL) inhibitors are associated with neutropenia, especially over the first months of treatment. Anti-CD20 agents may cause defects in the adaptative immune response, hypogammaglobulinemia, neutropenia, and hepatitis B reactivation. Alemtuzumab is associated with profound and long-lasting immunosuppression; screening is recommended for latent infections and prevention strategies against CMV, herpesvirus, and Pneumocystis infections. Checkpoint inhibitors (CIs) may cause immune-related adverse events for which prolonged treatment with corticosteroids is needed: prophylaxis against Pneumocystis is recommended.

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

“…Neutropenia [204,208] Surrogate markers such as Serum or Bronchoalveolar Lavage Galactomannan Assay [209][210][211] Haematopoietic stem cell transplantation [204,208,212] Solid organ transplantation [202,[212][213][214] High dose corticosteroid therapy [215,216] Certain biologic response modifiers [206,217,218] outweigh the potential benefits [322]. Limited data on the cost-effectiveness are available, although a single centre study reported decreased hospital costs associated with PCT-guided antibiotic in medical ICU patient with undifferentiated sepsis [323].…”

Cytomegalovirus‐specific T‐cell immunity and DNAemia in patients with chronic lymphocytic leukaemia undergoing treatment with ibrutinib

“…1 Ibrutinib targets Bruton tyrosine kinase (BTK), which plays a major role in B-and T-cell proliferation and survival 2 and recognition of infectious agents by the innate immune system. 3 Ibrutinib therapy has been associated with an increased incidence of several opportunistic infections, especially in the first 6-12 months after therapy initiation, [4][5][6][7] among which cytomegalovirus (CMV) end-organ disease has been anecdotally reported. 8 Nevertheless, little is known about the biology of CMV in ibrutinib-treated patients.…”

mTOR-regulated Mitochondrial Metabolism Limits Mycobacterium-induced Cytotoxicity

“…The association of infections, including TB, with therapeutic mTOR blockade in organ transplantation and cancer is well recognized (Fijalkowska-Morawska et al, 2011; Garcia and Wu, 2016; Jeon et al, 2017; Ruiz-Camps and Aguilar-Company, 2021; Tsai et al, 2007). Since mTOR signaling in phagocytes, antigen-presenting cells, and T cells is critical for their development, homeostasis and/or function, it is likely that mTOR exerts its protective effects in TB through a myriad of mechanisms impacting innate and adaptive immune responses (Lachmandas et al, 2016; Powell et al, 2012; Sinclair et al ., 2017; Weichhart et al ., 2015).…”