Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study.

OBJECTIVES: To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels of antibodies to the receptor-binding domain of SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. METHODS: IMIDs on immunosuppressives and healthy controls (HC) receiving SARS-CoV-2 vaccines were included in this prospective observational study. COVID-19 and outcome were registered and anti-RBD antibodies measured 2-5 weeks post-immunisation. RESULTS: Between 15 February 2021 and 15 February 2023, 1729 IMIDs and 350 HC provided blood samples and self-reported COVID-19. The incidence of COVID-19 was 66% in patients and 67% in HC, with re-infection occurring in 12% of patients. Severe COVID-19 was recorded in 22 (2%) patients and no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk of COVID-19 (HR 5.89 (95% CI 4.45 to 7.80)) than hybrid immunity. Post-immunisation anti-RBD levels <6000 binding antibody units/mL were associated with an increased risk of COVID-19 following three (HR 1.37 (95% CI 1.08 to 1.74)) and four doses (HR 1.28 (95% CI 1.02 to 1.62)), and of COVID-19 re-infection (HR 4.47 (95% CI 1.87 to 10.67)). CONCLUSION: Vaccinated patients with IMID have a low risk of severe COVID-19. Hybrid immunity lowers the risk of infection. High post-immunisation anti-RBD levels protect against COVID-19. These results suggest that knowledge on COVID-19 history, and assessment of antibody levels post-immunisation can help individualise vaccination programme series in high-risk individuals. TRIAL REGISTRATION NUMBER: NCT04798625.

EFFECT OF SOME IMMUNOMODULATORY DRUGS ON EMBRYONIC DEVELOPMENT OF DANIO RERIO FISH.

At the current stage of healthcare development, the inclusion of immunomodulators in the complex pharmacotherapy of various immunoinflammatory and viral diseases is widely discussed, but due to the lack of sufficient research and a broad evidence base, not all drugs with similar properties are used in medicine. According to the information obtained from the instructions for the use of immunomodulators, it was obtained that the main contraindications to their use include the prescription of children, pregnant women, and women during breastfeeding. In this study, we evaluated the effects of immunomodulatory drugs: aminodihydrophthalazindione sodium and meglumine acridonacetate, on the early developmental stages of Danio rerio (Zebrafish) embryos.

A novel T cell-redirecting anti-GPRC5D × CD3 bispecific antibody with potent antitumor activity in multiple myeloma preclinical models.

G-protein-coupled receptor class 5 member D (GPRC5D) is detected in malignant plasma cells in approximately 90% of patients diagnosed with multiple myeloma (MM). Here, we constructed BsAb5003, a novel humanized bispecific monoclonal antibody targeting CD3 and GPRC5D, and evaluated its therapeutic impact on MM. BsAb5003 induced specific cytotoxicity of GPRC5D-positive MM cells with concomitant T cell activation and cytokine release. The efficacy of BsAb5003 was associated with GPRC5D expression levels in MM cell lines. Flow cytometry analysis of bone marrow mononuclear cells (BMMNCs) from 49 MM patients revealed that GPRC5D was expressed in a wide population of MM patients, including heavily treated and high-risk patients. In ex vivo assays using BMMNCs, BsAb5003 induced potent efficacy against CD138 + MM cells in both newly diagnosed and relapsed/refractory patient samples in a GPRC5D expression-dependent manner. BsAb5003 significantly enhanced T cell activation and cytokine production in combination with immunomodulatory drugs (IMiDs) against MM cell lines. BsAb5003 also demonstrated significant inhibition of in vivo tumor growth by recruiting T cells. Taken together, these results suggest that T cell-redirecting bispecific antibody targeting GPRC5D as monotherapy and combination therapy with IMiDs could be a highly potent and effective treatment approach for a wide population of MM patients.

scDrugPrio: a framework for the analysis of single-cell transcriptomics to address multiple problems in precision medicine in immune-mediated inflammatory diseases.

BACKGROUND: Ineffective drug treatment is a major problem for many patients with immune-mediated inflammatory diseases (IMIDs). Important reasons are the lack of systematic solutions for drug prioritisation and repurposing based on characterisation of the complex and heterogeneous cellular and molecular changes in IMIDs. METHODS: Here, we propose a computational framework, scDrugPrio, which constructs network models of inflammatory disease based on single-cell RNA sequencing (scRNA-seq) data. scDrugPrio constructs detailed network models of inflammatory diseases that integrate information on cell type-specific expression changes, altered cellular crosstalk and pharmacological properties for the selection and ranking of thousands of drugs. RESULTS: scDrugPrio was developed using a mouse model of antigen-induced arthritis and validated by improved precision/recall for approved drugs, as well as extensive in vitro, in vivo, and in silico studies of drugs that were predicted, but not approved, for the studied diseases. Next, scDrugPrio was applied to multiple sclerosis, Crohn's disease, and psoriatic arthritis, further supporting scDrugPrio through prioritisation of relevant and approved drugs. However, in contrast to the mouse model of arthritis, great interindividual cellular and gene expression differences were found in patients with the same diagnosis. Such differences could explain why some patients did or did not respond to treatment. This explanation was supported by the application of scDrugPrio to scRNA-seq data from eleven individual Crohn's disease patients. The analysis showed great variations in drug predictions between patients, for example, assigning a high rank to anti-TNF treatment in a responder and a low rank in a nonresponder to that treatment. CONCLUSIONS: We propose a computational framework, scDrugPrio, for drug prioritisation based on scRNA-seq of IMID disease. Application to individual patients indicates scDrugPrio's potential for personalised network-based drug screening on cellulome-, genome-, and drugome-wide scales. For this purpose, we made scDrugPrio into an easy-to-use R package ( https://github.com/SDTC-CPMed/scDrugPrio ).

Equity, expense, and expertise in biologic commissioning: adding the patient to the equation.

INTRODUCTION: Immune-mediated inflammatory diseases (IMIDs) are increasingly managed effectively with biologic medicines. However, with relatively high unit costs, there remains a meaningful pressure to ensure streamlined, equitable, and inclusive prescription of biologics in the UK. Despite an increased awareness of the benefits of patient-centric shared decision making, patients remain on the periphery of biologic selection for the treatment of IMIDs. AREAS COVERED: We provide a patient perspective on core issues in the commissioning, prescription, and decision making around biologics for IMIDs in the UK, focusing on England. In particular, the crucial aspect of determining 'value' for different stakeholders, who necessarily have different priorities, is considered. EXPERT OPINION: There are disparities in commissioning, access to, and prescription of biologics for IMIDs in the UK. This creates an unequal treatment model and drives patient dissatisfaction with an 'experience lottery' for the management of disease. A more transparent approach to prescribing decisions, made in close consultation with patients, is essential for improving equity and experience with biologic treatment of IMIDs.

Outcome Reporting Bias in Clinical Trials Researching Disease-Modifying Therapy in Patients With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Outcome reporting bias occurs when publication of trial results is dependent on clinical significance, thereby threatening the validity of trial results. Research on immunomodulatory drugs in multiple sclerosis has thrived in recent years. We aim to comprehensively examine to what extent outcome reporting bias is present in these trials and the possible underlying factors. METHODS: We identified clinical trials evaluating the efficacy and safety of immunomodulatory drugs in patients with multiple sclerosis (MS) registered in ClinicalTrials.gov after September 2007 and completed before the end of 2018. Information about study design, type of funding, and primary and secondary outcome measures was extracted from the registry. Timing of registration in relation to study initiation and subsequent amendments to the planned outcomes were reviewed. Publications related to these trials were identified in several bibliographic databases using the trial registration number. Registered primary and secondary outcomes were recorded for each trial and compared with outcomes in the publication describing the main outcomes of the trial. RESULTS: A search of ClinicalTrials.gov identified 535 eligible registered clinical trials; of these, 101 had a matching publication. Discrepancies between registered and published primary and secondary outcomes were found in 95% of the trials, including discrepancies between the registered and published primary outcomes in 26 publications. Forty-four percent of the published secondary outcomes were not included in the registry. A similar proportion of registered and nonregistered reported primary efficacy outcomes were positive (favoring the intervention). Nonindustry-funded and open-label trials in MS were more prone to selective primary outcome reporting, although these findings did not reach statistical significance. Only two-thirds of the trials were registered in ClinicalTrials.gov before the trial start date, and 62% of trials made amendments in registered outcomes during or after the trial period. DISCUSSION: Selective outcome reporting is prevalent in trials of disease-modifying drugs in people with MS. We propose methods to diminish the occurrence of this bias in future research.

The effect of immunomodulatory drugs on bone metabolism of patients with multiple myeloma.

INTRODUCTION: Immunomodulatory drugs (IMiDs) are widely used in the management of newly diagnosed and relapsed/refractory multiple myeloma patients. These agents show their potential effect on myeloma bone disease (MBD), including inhibition of osteoclasts activity and effects on osteoblasts differentiation. It is unclear whether these effects are direct, which may have an impact on bone formation markers when combined with proteasome inhibitors. AREAS COVERED: This review summarizes the available evidence on the role of IMiDs in microenvironment regulation and their potential effects on bone metabolism. The literature search methodology consisted of searching PubMed for basic and clinical trials using medical subject terms. Included articles were screened and evaluated by the coauthors of this review. EXPERT OPINION: As a therapeutic option, IMiDs directly affect preosteoblast/osteoclast differentiation. The combination of proteasome inhibitors may counteract the short-term up-regulation of osteogenic activity markers, and therefore intravenous zoledronic acid is recommended, however, obtaining a more significant myeloma response will have a long-term positive impact on myeloma bone disease.

Thrombospondin-1 is an endogenous substrate of cereblon responsible for immunomodulatory drug-induced thromboembolism.

ABSTRACT: Immunomodulatory drugs (IMiDs) are key drugs for treating multiple myeloma and myelodysplastic syndrome with chromosome 5q deletion. IMiDs exert their pleiotropic effects through the interaction between cell-specific substrates and cereblon, a substrate receptor of the E3 ubiquitin ligase complex. Thus, identification of cell-specific substrates is important for understanding the effects of IMiDs. IMiDs increase the risk of thromboembolism, which sometimes results in fatal clinical outcomes. In this study, we sought to clarify the molecular mechanisms underlying IMiDs-induced thrombosis. We investigated cereblon substrates in human megakaryocytes using liquid chromatography-mass spectrometry and found that thrombospondin-1 (THBS-1), which is an inhibitor of a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13, functions as an endogenous substrate in human megakaryocytes. IMiDs inhibited the proteasomal degradation of THBS-1 by impairing the recruitment of cereblon to THBS-1, leading to aberrant accumulation of THBS-1. We observed a significant increase in THBS-1 in peripheral blood mononuclear cells as well as larger von Willebrand factor multimers in the plasma of patients with myeloma, who were treated with IMiDs. These results collectively suggest that THBS-1 represents an endogenous substrate of cereblon. This pairing is disrupted by IMiDs, and the aberrant accumulation of THBS-1 plays an important role in the pathogenesis of IMiDs-induced thromboembolism.

Prevalence of Pretreatment Testing Recommended for Patients With Chronic Inflammatory Skin Diseases.

Importance: Laboratory testing for the presence of tuberculosis, hepatitis, and other conditions before starting most systemic immunomodulatory agents is recommended in patients with chronic inflammatory skin diseases (CISD) but current testing patterns in the US are unclear. Objective: To determine the prevalence of pretreatment testing that is recommended for patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis). Design, Setting, and Participants: This descriptive analysis of US commercial insurance claims databases from December 31, 2002, to December 31, 2020, included adult patients with CISD (psoriasis, hidradenitis suppurativa, or atopic dermatitis) who started an immunomodulatory agent, including methotrexate, tumor necrosis factor α inhibitors, interleukin (IL)-17Ai, ustekinumab, IL-23i, dupilumab, or apremilast. Main Outcomes and Measures: The proportion of patients who underwent the screening tests as suggested by professional societies-including for tuberculosis, hepatitis, and liver function; complete blood cell counts; and lipid panels-were determined within 6 months before and during 2 years after treatment start. Results: A total of 122 308 patients with CISDs (median [IQR] age, 49 [38-58] years; 63 663 [52.1%] male) starting systemic immunomodulatory treatment in the US were included. Treatment for patients with CISDs comprised methotrexate (28 684), tumor necrosis factor α inhibitors (40 965), ustekinumab (12 841), IL-23i (6116), IL-17Ai (9799), dupilumab (7787), or apremilast (16 116). Complete blood cell count was the most common test, performed in 41% (3161/7787) to 69% (19 659/28 684) of individuals before initiation across treatments. Between 11% (889/7787) and 59% (3613/6116) of patients had tuberculosis screening within 6 months before treatment, and 3% (149/4577) to 26% (1559/6097) had updated tests 1 year later. Between 13% (1006/7787) and 41% (16 728/40 965) had hepatitis panels before treatment. Low pretreatment testing levels before apremilast (15% [2331/16 116] to 45% [7253/16 116]) persisted a year into treatment (9% [816/8496] to 36% [2999/8496]) and were similar to dupilumab (11% [850/7787] to 41% [3161/7787] vs 3% [149/4577] to 25% [1160/4577]). Conclusions and Relevance: In this descriptive analysis of patients with CISDs starting systemic immunomodulatory treatment in the US, less than 60% received the recommended pretreatment testing. Additional research is required to understand whether variations in testing affect patient outcomes.

Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

Focused ultrasound-assisted delivery of immunomodulating agents in brain cancer.

Focused ultrasound (FUS) combined with intravascularly circulating microbubbles can transiently increase the permeability of the blood-brain barrier (BBB) to enable targeted therapeutic delivery to the brain, the clinical testing of which is currently underway in both adult and pediatric patients. Aside from traditional cancer drugs, this technique is being extended to promote the delivery of immunomodulating therapeutics to the brain, including antibodies, immune cells, and cytokines. In this manner, FUS approaches are being explored as a tool to improve and amplify the effectiveness of immunotherapy for both primary and metastatic brain cancer, a particularly challenging solid tumor to treat. Here, we present an overview of the latest groundbreaking research in FUS-assisted delivery of immunomodulating agents to the brain in pre-clinical models of brain cancer, and place it within the context of the current immunotherapy approaches. We follow this up with a discussion on new developments and emerging strategies for this rapidly evolving approach.

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are recognised risk factors for accelerated atherosclerotic cardiovascular disease (CVD), particularly in younger individuals and women who lack traditional CVD risk factors. Reflective of the critical role that inflammation plays in the formation, progression and rupture of atherosclerotic plaques, research into immune mechanisms of CVD has led to the identification of a range of therapeutic targets that are the subject of ongoing clinical trials. Several key inflammatory pathways implicated in the pathogenesis of atherosclerosis are targeted in people with IMIDs. However, cardiovascular risk continues to be systematically underestimated by conventional risk assessment tools in the IMID population, resulting in considerable excess CVD burden and mortality. Hence, there is a pressing need to improve methods for CVD risk-stratification among patients with IMIDs, to better guide the use of statins and other prognostic interventions. CT coronary angiography (CTCA) is the current first-line investigation for diagnosing and assessing the severity of coronary atherosclerosis in many individuals with suspected angina. Whether CTCA is also useful in the general population for reclassifying asymptomatic individuals and improving long-term prognosis remains unknown. However, in the context of IMIDs, it is conceivable that the information provided by CTCA, including state-of-the-art assessments of coronary plaque, could be an important clinical adjunct in this high-risk patient population. This narrative review discusses the current literature about the use of coronary CT for CVD risk-stratification in three of the most common IMIDs including rheumatoid arthritis, psoriasis and systemic lupus erythematosus.

Racial/ethnic differences in autoimmune disease prevalence in US claims/EHR data.

OBJECTIVES: Few studies have evaluated racial and ethnic differences in several immune-mediated inflammatory diseases (IMIDs) or overlap syndrome (the co-occurrence of ≥ 2 IMIDs). We assessed associations between race and ethnicity and prevalence of IMIDs and overlap syndrome using US claims and electronic health records from 2021. STUDY DESIGN: Retrospective cohort study of 10.8 million adults. METHODS: We identified the 10 most prevalent IMIDs among frequently discussed IMIDs. We estimated associations between the 5 most prevalent IMIDs and overlap syndrome in Hispanic and non-Hispanic Asian and Black adults using non-Hispanic White adults as the referent and stratifying by sex and age (20-39, 40-59, and ≥ 60 years). RESULTS: Inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and rheumatoid arthritis (RA) were the most prevalent IMIDs in all races and ethnicities. We observed positive associations (P < .0001) between Hispanic and non-Hispanic Black adults and SLE, Asian women of all ages and Asian men younger than 60 years and SLE, Black women younger than 60 years and MS, and Hispanic and non-White women 60 years or older and RA. Hispanic and non-White adults of all age groups had inverse associations (P < .0001) with IBD. Non-Hispanic Black adults of all ages and Hispanic and non-Hispanic Asian women 40 years or older had inverse associations (P < .0001) with psoriasis/psoriatic arthritis. Overlap syndrome was rare among all groups, with some variation in which IMIDs co-occurred. CONCLUSIONS: We found racial and ethnic differences in the prevalence and co-occurrence of IMIDs in this sample of US adults. Because misdiagnoses are relatively frequent for patients with IMIDs, awareness of racial and ethnic variations in IMIDs could aid early diagnosis and improve disease management.

Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

Characterization of immunomodulating agents from Staphylococcus aureus for priming immunotherapy in triple-negative breast cancers.

Immunotherapy, specifically immune checkpoint blockade (ICB), has revolutionized the treatment paradigm of triple-negative breast cancers (TNBCs). However, a subset of TNBCs devoid of tumor-infiltrating T cells (TILs) or PD-L1 expression generally has a poor response to immunotherapy. In this study, we aimed to sensitize TNBCs to ICB by harnessing the immunomodulating potential of S. aureus, a breast-resident bacterium. We show that intratumoral injection of spent culture media from S. aureus recruits TILs and suppresses tumor growth in a preclinical TNBC model. We further demonstrate that α-hemolysin (HLA), an S. aureus-produced molecule, increases the levels of CD8+ T cells and PD-L1 expression in tumors, delays tumor growth, and triggers tumor necrosis. Mechanistically, while tumor cells treated with HLA display Gasdermin E (GSDME) cleavage and a cellular phenotype resembling pyroptosis, splenic T cells incubated with HLA lead to selective expansion of CD8+ T cells. Notably, intratumoral HLA injection prior to ICB augments the therapeutic efficacy compared to ICB alone. This study uncovers novel immunomodulatory properties of HLA and suggests that intratumoral administration of HLA could be a potential priming strategy to expand the population of TNBC patients who may respond to ICB.

Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis.

Psoriasis and atopic dermatitis fall within the category of cutaneous immune-mediated inflammatory diseases (IMIDs). The prevalence of IMIDs is increasing in industrialized societies, influenced by both environmental changes and a genetic predisposition. However, the exact immune factors driving these chronic, progressive diseases are not fully understood. By using multi-omics techniques in cutaneous IMIDs, it is expected to advance the understanding of skin biology, uncover the underlying mechanisms of skin conditions, and potentially devise precise and personalized approaches to diagnosis and treatment. We provide a narrative review of the current knowledge in genomics, epigenomics, and proteomics of atopic dermatitis and psoriasis. A literature search was performed for articles published until 30 November 2023. Although there is still much to uncover, recent evidence has already provided valuable insights, such as proteomic profiles that permit differentiating psoriasis from mycosis fungoides and ß-defensin 2 correlation to PASI and its drop due to secukinumab first injection, among others.

Elotuzumab: Empiric analysis of dexamethasone administration schedule.

Elotuzumab in combination with dexamethasone and immunomodulating agents (IMiDs) lenalidomide or pomalidomide is 2nd to 4th line therapy for multiple myeloma. The labelled dosage of dexamethasone for use in conjunction with elotuzumab and IMiDs splits the dexamethasone dose into two administrations, one oral and one intravenous, on the days of each elotuzumab infusion. Administration of split dose dexamethasone on days of elotuzumab administration is based on the registration trials submitted for drug approval and was intended to ensure standard well-timed immunotherapy premedication using pharmacologically equivalent dexamethasone doses for both study arms. Administration of dexamethasone in the manner delineated by the elotuzumab product label adds complexity to the delivery of care. This commentary provides an empirical assessment of established medication safety and effectiveness which supports administration of dexamethasone standard intermittent dose instead of the split dose approach delineated on elotuzumab package insert. Simplification of regimen administration improves medication adherence, reduces the risk of inadvertent omission or duplication of medication therapy, and improves the workflow required for delivery of care.

Designing Hydrogels for Immunomodulation in Cancer Therapy and Regenerative Medicine.

The immune system not only acts as a defense against pathogen and cancer cells, but also plays an important role in homeostasis and tissue regeneration. Targeting immune systems is a promising strategy for efficient cancer treatment and regenerative medicine. Current systemic immunomodulation therapies are usually associated with low persistence time, poor targeting to action sites, and severe side effects. Due to their extracellular matrix-mimetic nature, tunable properties and diverse bioactivities, hydrogels are intriguing platforms to locally deliver immunomodulatory agents and cells, as well as provide an immunomodulatory microenvironment to recruit, activate, and expand host immune cells. In this review, the design considerations, including polymer backbones, crosslinking mechanisms, physicochemical nature, and immunomodulation-related components, of the hydrogel platforms, are focused on. The immunomodulatory effects and therapeutic outcomes in cancer therapy and tissue regeneration of different hydrogel systems are emphasized, including hydrogel depots for delivery of immunomodulatory agents, hydrogel scaffolds for cell delivery, and immunomodulatory hydrogels depending on the intrinsic properties of materials. Finally, the remained challenges in current systems and future development of immunomodulatory hydrogels are discussed.