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Cytomegalovirus (CMV) infection/disease has been repeatedly reported in patients treated with immune-checkpoint inhibitors (ICIs) and most commonly involves patients with relapsed/refractory (R/R) immune-related adverse events (irAEs). In the current study, we present a patient with melanoma who developed CMV gastritis during treatment with pembrolizumab in the absence of irAEs and without previous or current immunosuppression. Moreover, we review the literature regarding CMV...

Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance. Administration of eculizumab has been reported to...

Abstract Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients.

Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reporting on invasive fungal infections (IFI) associated with ibrutinib administration. We conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. One-hundred-thirteen patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed,...

Tyrosine kinases inhibitors (TKIs) are small molecules that have been developed as targeted therapies for various medical conditions. They act specifically on tyrosine kinases, a family of membrane-bound or intracellular molecules that regulate a variety of important cellular functions. TKIs have emerged as treatment for hematologic malignancies and autoimmune diseases. Each class of TKI has unique features and often acts on a specific receptor, minimizing the risk of adverse effects and...

This review aims to analyze, from an infectious disease perspective, the safety profile of antineoplastic therapies targeting cell surface receptors and associated signaling pathways among cancer patients and to suggest recommendations.

Introduction and Aims: Inhibition of the IL-1 pathway has been the target of treatments for several inflammatory conditions. This clinical review aims to summarize the risk of infectious complications associated with the use of interleukin-1 (IL-1) targeted therapy.

Tumor necrosis factor-α (TNF-α) plays a central role in the immunopathogenesis of a wide variety of inflammatory conditions from diseases such as rheumatoid arthritis to inflammatory bowel diseases. Development of TNF-α inhibitors (TNFI) has revolutionized the ability to treat these conditions, resulting in substantial improvement in clinical outcomes. Since the introduction of infliximab and etanercept in 1998, indications for the use of TNFI have expanded, and these medications are...

This chapter is focused on the agents targeting lymphoid and myeloid cell surface antigens CD22, CD30, CD33, CD38, CD40, SLAMF-7 (CD319), and CCR-4. Over the past 20 years, many monoclonal antibodies targeting these antigens have been developed and introduced into clinical practice. Many of them are used successfully for the treatment of leukemia, lymphoma, multiple myeloma, and systemic autoimmune diseases (e.g. systemic lupus erythematosus, Sjogren’s syndrome) both in monotherapy and in...

The role of the structurally related interleukin-(IL) 12 and IL-23, as key drivers of Th1 and Th17 differentiation, in the pathogenesis of inflammatory chronic conditions has led to the development of various monoclonal antibodies targeted either at the common p40 subunit shared both cytokines (ustekinumab) or at the IL-23-specific p19 subunit (guselkumab, tildrakizumab, and risankizumab). These IL-12/23-targeted agents are currently approved for the treatment of plaque psoriasis, psoriatic...

Sphingosine-1-phosphate receptor (S1PR) modulators have and are being evaluated for numerous conditions. To date, the main indication of this group of drugs is for multiple sclerosis (MS). Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS) leading to demyelination and neurodegeneration. Therapeutic approaches are focused on both inflammation and neurodegeneration that are present from early stages of the disease. Sphingosine-1-phosphate receptor (S1PR)...

Integrins are transmembrane receptors that play a key role in cell adhesion and intracellular signaling. Leukocyte integrins are essential for the recruitment of leukocytes from the vasculature to the tissues and are used as therapeutic targets to modulate inflammation. The monoclonal antibody natalizumab targets the α4 subunit of α4β1 and α4β7 integrins, implicated in the entry of lymphocytes in the central nervous system (CNS) and the gut mucosa, respectively. These integrins are involved...

Immune costimulatory checkpoints are crucial in regulating both lymphocyte activation and function. They also serve a major role in foreign antigen specificity and self-tolerance. The two major families of checkpoint inhibitors target the CTLA-4/B7s and the PD-1/PD-L1 axis. Inhibition of either of these two pathways intends to enhance the antitumor activity of lymphocytes. The risk of infections associated with checkpoint inhibition can be explained by two major mechanisms: the use of...

The 9th web-based European Conference on Infections in Leukemia (ECIL-9), held September 16-17, 2021, reviewed the risk of infections and febrile neutropenia associated with more recently approved immunotherapeutic agents and molecular targeted drugs for the treatment of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Novel antibody based treatment approaches (inotuzumab ozogamicin, gemtuzumab ozogamicin, flotetuzumab), isocitrate dehydrogenases inhibitors (ivosidenib,...

Agents targeting the CD19, CD20 and CD52 surface antigens on lymphoid cells have been increasingly used in the past three decades in various haematologic, rheumatologic and autoimmune diseases. The impact these agents have on the immune system and their consequent infectious complications depend on the agent, dose, underlying disease and concomitant or previous immunosuppressive treatments.

Small-molecule inhibitors have revolutionized the treatment of cancer and autoimmune disease. Inhibitors of the mammalian target of rapamycin (mTOR), Janus kinases (JAK), and B-cell lymphoma-2 (BCL-2) are three of the most successful therapeutics developed. They target intracellular signaling pathways involved in cell survival, proliferation, and metabolism, processes that are frequently dysregulated in autoimmunity and neoplasia. The inhibition of such pathways also affects physiological...

Chimeric antigen receptor (CAR) T cells targeting the B-cell-specific antigen, CD19, has revolutionized the management and prognosis of patients with relapsing/refractory B-cell malignancies. Such patients often present immunosuppressed due to previous treatments and baseline malignancy. Lymphodepletion chemotherapy is administered prior to CAR T therapy, causing profound cytopenias and mucositis. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome...

IL-6 has a key role in supporting immunocompetent responses to all type of infections, especially bacterial events. Agents targeting IL-6 and/or its receptor may result in severe and potentially life-threatening infections with significant discrepancy in both clinical and laboratory markers. Current evidence on the infection risk associated with the use of IL-6 or IL-6R-targeted agents consists mostly of studies including patients treated for a chronic autoimmune condition, such as...

Background.  Tocilizumab is an interleukin-6 receptor antagonist recently described as a promising treatment for antibody-mediated rejection. We compared infectious complications among tocilizumab-treated kidney transplant patients with those receiving intravenous immunoglobulin (IVIG)/rituximab. Methods.  Infections occurring among 148 kidney recipients treated with tocilizumab 8 mg/kg IV monthly (n = 83) or IVIG/rituximab (n = 65) for donor-specific antibodies and...