Tapering thrombopoietin receptor agonists in primary immune thrombocytopenia: Expert consensus based on the RAND/UCLA modified Delphi panel method.

Background: Thrombopoietin receptor agonists (TPO-RAs) are used to treat primary immune thrombocytopenia (ITP). Some patients have discontinued treatment while maintaining a hemostatic platelet count.

Objectives: To develop expert consensus on when it is appropriate to consider tapering TPO-RAs in ITP, how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy.

Baseline Plasma Tumor Mutation Burden Predicts Response to Pembrolizumab-based Therapy in Patients with Metastatic Non-Small Cell Lung Cancer.

Purpose: The role of plasma-based tumor mutation burden (pTMB) in predicting response to pembrolizumab-based first-line standard-of-care therapy for metastatic non-small cell lung cancer (mNSCLC) has not been explored.

Experimental Design: A 500-gene next-generation sequencing panel was used to assess pTMB. Sixty-six patients with newly diagnosed mNSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy, were enrolled (Clinicaltrial.

Epacadostat Plus Pembrolizumab in Patients With Advanced Solid Tumors: Phase I Results From a Multicenter, Open-Label Phase I/II Trial (ECHO-202/KEYNOTE-037).

Purpose: Tumors may evade immunosurveillance through upregulation of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. Epacadostat is a potent and highly selective IDO1 enzyme inhibitor. The open-label phase I/II ECHO-202/KEYNOTE-037 trial evaluated epacadostat plus pembrolizumab, a programmed death protein 1 inhibitor, in patients with advanced solid tumors.

Systematic literature review of treatments used for adult immune thrombocytopenia in the second-line setting.

Immune thrombocytopenia (ITP) is a rare platelet disorder that is often persistent or chronic in adults. Patient management is dependent upon physician judgment and patient preference, given both the rarity of the condition and a paucity of high-quality clinical trial evidence to inform practice guidelines. A systematic literature review was conducted to provide an up-to-date summary of studies evaluating the safety and efficacy/effectiveness of therapies used to treat adults with primary ITP in the second-line setting.

A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice.

Combination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, "OrthomAb", is shown.

Rate of bleeding-related episodes in elderly patients with primary immune thrombocytopenia: a retrospective cohort study.

Objective: Immune thrombocytopenia (ITP) is characterized by low platelet counts and a tendency toward increased bleeding and bruising. We aimed to describe bleeding frequency and use of rescue ITP therapy to treat or prevent bleeding in elderly ITP patients in a real-world setting.

Methods: Using Medicare 20% sample data, 2007-2012, we identified elderly (ages ≥67 years) Medicare fee-for-service enrollees diagnosed with primary ITP between 1 January 2009 and 30 September 2012.

Cost of Bleeding-related Episodes in Adult Patients With Primary Immune Thrombocytopenia: A Population-based Retrospective Cohort Study of Administrative Claims Data for Commercial Payers in the United States.

Purpose: We estimated the real-world costs of bleeding-related episodes (BREs) in adults with primary immune thrombocytopenia (ITP).

Methods: This retrospective cohort study used the MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. We identified adult patients diagnosed with primary ITP between 2007 and 2012, defined by at least 2 outpatient claims separated by ≥30 days or 1 inpatient claim (International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code for primary ITP [287.

Cytokines and metabolic factors regulate tumoricidal T-cell function during cancer immunotherapy.

Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Rate of bleeding-related episodes in adult patients with primary immune thrombocytopenia: a retrospective cohort study using a large administrative medical claims database in the US.

Background: Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. The goal of ITP therapy is to treat or prevent bleeding. Actual rates of bleeding are unknown.

Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too?

Introduction: Monoclonal antibodies (mAbs) targeting checkpoint inhibitors have demonstrated clinical benefit in treating patients with cancer and have paved the way for additional immune-modulating mAbs such as those targeting costimulatory receptors. The full clinical utility of these agents, however, is hampered by immune-related adverse events (irAEs) that can occur during therapy.

Areas Covered: We first provide a general overview of tumor immunity, followed by a review of the two major classes of immunomodulatory mAbs being developed as cancer therapeutics: checkpoint inhibitors and costimulatory receptor agonists.

Tumor-Unrelated CD4 T Cell Help Augments CD134 plus CD137 Dual Costimulation Tumor Therapy.

The ability of immune-based cancer therapies to elicit beneficial CD8(+) CTLs is limited by tolerance pathways that inactivate tumor-specific CD4 Th cells. A strategy to bypass this problem is to engage tumor-unrelated CD4 Th cells. Thus, CD4 T cells, regardless of their specificity per se, can boost CD8(+) CTL priming as long as the cognate epitopes are linked via presentation on the same dendritic cell.

Targeting HER2 in the treatment of non-small cell lung cancer.

Oncogenic driver mutations have emerged as major treatment targets for molecular therapies in a variety of cancers. HER2 positivity has been well-studied in breast cancer, but its importance is still being explored in non-small cell lung cancer (NSCLC). Laboratory methods for assessment of HER2 positivity in NSCLC include immunohistochemistry (IHC) for protein overexpression, fluorescent in situ hybridization (FISH) for gene amplification, and next generation sequencing (NGS) for gene mutations.

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial.

Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP.

AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP.

Background: Most current treatments for chronic immune thrombocytopenic purpura (ITP) act by decreasing platelet destruction. In a phase 1-2 study, we administered a thrombopoiesis-stimulating protein, AMG 531, to patients with ITP.

Methods: In phase 1, 24 patients who had received at least one treatment for ITP were assigned to escalating-dose cohorts of 4 patients each and given two identical doses of AMG 531 (0.