Risk of Infection with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis
Posted: Sun Apr 24, 2022 11:11 am
Risk of Infection with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis
Introduction
An impaired immune response and the loss of barrier integrity due to tumor development and treatments (e.g., those causing myelosuppression) render cancer patients more susceptible to infections. Infections and neutropenia represent some of the most common life-threatening side effects, generating higher mortality and morbidity in patients who are treated with chemotherapy (CT) [1]. Diverse clinical factors identify the patients who have a high risk of developing neutropenia. These factors include: older age, advanced disease, poor performance status, the nature of the anti-cancer treatment, concomitant steroid use, no granulocyte colony-stimulating factor (G-CSF) use, underlying chronic lung disease, and hepatic or renal insufficiency [2].
Immune checkpoint inhibitors (ICIs) boost the spontaneous, pre-existing, adaptive anti-tumor immune response by rescuing the activity of the patients' dysfunctional immune cells. The most common adverse events (AEs) linked to ICIs have an autoimmune-like hyperactivation genesis. Interestingly, a stimulus to the function of the T helper-1 (Th1) cells could be responsible for the sporadic reactivation of tuberculosis, as found in several patients who were treated with anti-programmed cell death-1 (PD-1) antibodies [3, 4]. Additionally, a retrospective study on melanoma patients revealed that the immunosuppressive drugs employed for the management of immune-related AEs (e.g., steroids and the tumor necrosis factor-alpha (TNF-α) inhibitor infliximab) represent the main risk factors for the development of infections in patients undergoing ICIs [5]. Furthermore, a recent meta-analysis revealed that patients with solid tumors who were treated with ICIs were less likely to develop severe AEs than those receiving CT [6].
Currently, ICIs are being used either alone or in combination with other agents, such as CT, and the risk of infection in these patients is unknown. It is not clear which agents (e.g., bacteria, virus, and fungi) or which sites (e.g., lung, urinary system, gastrointestinal tract, skin, etc.) are most associated with infections in patients treated with ICIs.
We performed this systematic review and meta-analysis to evaluate the incidence, grade (G), and relative risk (RR) of infection in patients with solid tumors who were enrolled in randomized trials and receiving ICIs as single agents or in combination with CT versus other treatments (e.g., CT and placebo).https://www.ncbi.nlm.nih.gov/pmc/articl ... FPar1title
Introduction
An impaired immune response and the loss of barrier integrity due to tumor development and treatments (e.g., those causing myelosuppression) render cancer patients more susceptible to infections. Infections and neutropenia represent some of the most common life-threatening side effects, generating higher mortality and morbidity in patients who are treated with chemotherapy (CT) [1]. Diverse clinical factors identify the patients who have a high risk of developing neutropenia. These factors include: older age, advanced disease, poor performance status, the nature of the anti-cancer treatment, concomitant steroid use, no granulocyte colony-stimulating factor (G-CSF) use, underlying chronic lung disease, and hepatic or renal insufficiency [2].
Immune checkpoint inhibitors (ICIs) boost the spontaneous, pre-existing, adaptive anti-tumor immune response by rescuing the activity of the patients' dysfunctional immune cells. The most common adverse events (AEs) linked to ICIs have an autoimmune-like hyperactivation genesis. Interestingly, a stimulus to the function of the T helper-1 (Th1) cells could be responsible for the sporadic reactivation of tuberculosis, as found in several patients who were treated with anti-programmed cell death-1 (PD-1) antibodies [3, 4]. Additionally, a retrospective study on melanoma patients revealed that the immunosuppressive drugs employed for the management of immune-related AEs (e.g., steroids and the tumor necrosis factor-alpha (TNF-α) inhibitor infliximab) represent the main risk factors for the development of infections in patients undergoing ICIs [5]. Furthermore, a recent meta-analysis revealed that patients with solid tumors who were treated with ICIs were less likely to develop severe AEs than those receiving CT [6].
Currently, ICIs are being used either alone or in combination with other agents, such as CT, and the risk of infection in these patients is unknown. It is not clear which agents (e.g., bacteria, virus, and fungi) or which sites (e.g., lung, urinary system, gastrointestinal tract, skin, etc.) are most associated with infections in patients treated with ICIs.
We performed this systematic review and meta-analysis to evaluate the incidence, grade (G), and relative risk (RR) of infection in patients with solid tumors who were enrolled in randomized trials and receiving ICIs as single agents or in combination with CT versus other treatments (e.g., CT and placebo).https://www.ncbi.nlm.nih.gov/pmc/articl ... FPar1title
met·a-a·nal·y·sis
/ˈmedəəˌnaləsəs/
nounSTATISTICS
examination of data from a number of independent studies of the same subject, in order to determine overall trends.
"an important component of meta-analysis is the investigation of the consistency of treatment effects across studies"