A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer.

LY3381916 is an orally available, highly selective, potent inhibitor of indoleamine 2,3-dioxygenase 1. This study explored the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of LY3381916 monotherapy and in combination with a programmed death-ligand 1 (PD-L1) inhibitor (LY3300054) in patients with advanced solid tumors. During dose escalation, patients received escalating doses of LY3381916 at 60-600 mg once daily (qd) and 240 mg twice daily in monotherapy (n=21) and in combination with PD-L1 inhibitor at 700 mg every 2 weeks (n=21).

Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody.

Purpose: T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM-3) blunts anticancer immunity and mediates resistance to programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors. We assessed a novel, first-in-class, TIM-3 mAb, LY3321367, alone or in combination with the anti-PD-L1 antibody, LY300054 in patients with advanced solid tumor.

Patients And Methods: This open-label, multicenter, phase Ia/b study aimed to define the safety/tolerability and recommended phase II dose (RP2D) of LY3321367 with or without LY300054.

Safety and Immunogenicity of LY3415244, a Bispecific Antibody Against TIM-3 and PD-L1, in Patients With Advanced Solid Tumors.

Purpose: Investigate the safety and efficacy of LY3415244, a TIM-3/PD-L1 bispecific antibody that blocks TIM-3 and PD-L1 in patients with advanced solid tumors.

Patients And Methods: A phase I, multicenter, open-label study was conducted in patients with advanced solid tumors. Patients were dosed every 2 weeks intravenously with flat doses of LY3415244 escalating from 3 to 70 mg.

BAT in the Diagnosis of Drug Allergy: a Novel Tool in Clinical Daily Practice?

Purpose Of Review: The aim of this study is to critically review the relevant literature published on basophil activation test, presenting the current knowledge and future perspectives.

Recent Findings: Basophil activation test (BAT) results varied accordingly to the class of the drug studied, and have promising results in immediate hypersensitivity reactions to pyrazolone (selective reactors), neuromuscular blockers, beta-lactams, and platinum compounds, all examples of classical IgE-mediated hypersensitivity drug reactions. Currently, BAT is applied in research settings, but based in the results of our review, the test can be considered as a diagnostic tool for daily practice for selected patients and selected drugs, when the test is available, particularly for patients who experienced severe reactions and when diagnosis cannot be stablished by serum-specific IgE and skin testing, in order to avoid unnecessary drug provocations tests.

Monoclonal Antibodies Hypersensitivity: Prevalence and Management.

The use of monoclonal antibodies (mAbs) has become broader because of their recognized effectiveness in the treatment of autoimmune, neoplastic, and inflammatory diseases. Consequently, hypersensitivity reactions (HSR) secondary to mAbs are being reported more often, and each mAb-related HSR presents specific features. This article discusses the main biological agents and associated HSR, the clinical presentation of such reactions, and the role of tryptase and skin testing in the diagnosis.

Current Knowledge and Management of Hypersensitivity Reactions to Monoclonal Antibodies.

Hypersensitivity reactions (HSRs) to monoclonal antibodies (mAbs) are increasingly frequent as this class of therapeutic agents is rapidly expanding. Immediate and nonimmediate HSRs have been reported with mAbs. Immediate HSRs can be explained by 3 main mechanisms: cytokine release syndrome, IgE-mediated, and IgG-mediated reactions.

Basophil Activation Test is a Relevant Biomarker of the Outcome of Rapid Desensitization in Platinum Compounds-Allergy.

Background: Rapid drug desensitization (RDD) has become a cornerstone in the management of immediate drug hypersensitivity reactions (DHRs) to chemotherapeutic agents. Because of the inherent risk of anaphylaxis during RDD, biomarkers to predict patients at risk of developing such severe reactions are needed. The basophil activation test (BAT) has been used in DHRs as a diagnostic tool.

Risk stratification and skin testing to guide re-exposure in taxane-induced hypersensitivity reactions.

Background: The optimal approach to patients with hypersensitivity reactions (HSRs) to taxanes has not been established.

Objective: We sought to assess the safety and efficacy of risk stratification based on the severity of the initial HSR and skin testing for guiding taxane reintroduction in patients with an HSR to these agents.

Methods: Data on 164 patients treated for a taxane-related HSR from April 2011 to August 2014 at the Dana-Farber Cancer Institute and Brigham and Women's Hospital were collected retrospectively.

Hypersensitivity to biological agents-updated diagnosis, management, and treatment.

Biological agents are used in the treatment of neoplastic, autoimmune, and inflammatory diseases and their clinical applications are becoming broader. Following their increased utilization, hypersensitivity reactions linked to these drugs have become more frequent, sometimes preventing the use of first-line therapies. The clinical presentation of hypersensitivity reactions to biological agents ranges from mild cutaneous manifestations to life-threatening reactions.

Perioperative anaphylaxis.

Perioperative anaphylaxis is a life-threatening condition with an estimated prevalence of 1:3,500 to 1:20,000 procedures and a mortality rate of up to 9 %. Clinical presentation involves signs such as skin rash, urticaria, angioedema, bronchospasm, tachycardia, bradycardia, and hypotension. Prompt recognition and treatment is of utmost importance to the patient's prognosis, since clinical deterioration can develop rapidly.