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Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).Die Multiple Sklerose ist eine komplexe, autoimmun vermittelte Erkrankung des zentralen Nervensystems, charakterisiert durch inflammatorische Demyelinisierung sowie axonalen/neuronalen Schaden. Die Zulassung verschiedener verlaufsmodifizierender Therapien und unser verbessertes Verständnis der Krankheitsmechanismen und -entwicklung in den letzten Jahren haben die Prognose und den Verlauf der Erkrankung deutlich verändert. Diese Aktualisierung der Behandlungsempfehlung der Multiple Sklerose Therapie Konsensus Gruppe konzentriert sich auf die wichtigsten Empfehlungen für verlaufsmodifizierende Therapien der Multiplen Sklerose im Jahr 2021. Unsere Empfehlungen basieren auf aktuellen wissenschaftlichen Erkenntnissen und gelten für diejenigen Medikamente, die in weiten Teilen Europas, insbesondere in den deutschsprachigen Ländern (Deutschland, Österreich, Schweiz), zugelassen sind.

The acute and long-lasting side effects of modern multimodal tumour therapy significantly impair quality of life and survival of patients afflicted with malignancies. The key components of this therapy include radiotherapy, conventional chemotherapy, immunotherapy and targeted therapies. In addition to established tumour therapy strategies, up to 30 new therapies are approved each year with only incompletely characterised side effects. This consensus paper discusses the risk factors that contribute to the development of a potentially adverse reaction to tumour therapy and, in addition, defines specific side effect profiles for different treatment groups. The focus is on novel therapeutics and recommendations for the surveillance and treatment of specific patient groups.

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals.

Bonertz, Andreas/0000-0002-6846-9265; Brough, Helen/0000-0001-7203-0813; Hoffmann, Hans Jurgen/0000-0002-6743-7931; Hoffmann-Sommergruber, Karin/0000-0002-8830-058X; Schmid-Grendelmeier, Peter/0000-0003-3215-3370 WOS:000569864500002 PubMed: 32306414 Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.

Interventional oncology is a subspecialty field of interventional radiology that addresses the diagnosis and treatment of cancer and cancer-related problems by using targeted minimally invasive procedures performed with image guidance. Immuno-oncology is an innovative area of cancer research and practice that seeks to help the patient’s own immune system fight cancer. Both interventional oncology and immuno-oncology can potentially play a pivotal role in cancer management plans when used alongside medical, surgical, and radiation oncology in the care of cancer patients. © RSNA, 2019

Background Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2–6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia. Body Management strategies for MCL are patient- and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available. Conclusion Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.

The last decade has seen improved outcomes for children requiring extracorporeal life support as well as for children undergoing hematopoietic cell transplantation. Thus, given the historically poor survival of hematopoietic cell transplantation patients using extracorporeal life support, the Pediatric Acute Lung Injury and Sepsis Investigators' hematopoietic cell transplantation and cancer immunotherapy subgroup aimed to characterize the utility of extracorporeal life support in facilitating recovery from critical cardiorespiratory illnesses in pediatric hematopoietic cell transplantation patients.All available published data were identified using a set of PubMed search terms for pediatric extracorporeal life support and hematopoietic cell transplantation.All articles that provided original reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support were included. Sixty-four manuscripts met search criteria. Twenty-four were included as primary reports of pediatric hematopoietic cell transplantation patients who underwent extracorporeal life support (11 were single case reports, four single institution case series, two multi-institution case series, and seven registry reports from Extracorporeal Life Support Organization, Pediatric Heath Information System, and Virtual Pediatric Systems).All 24 articles were reviewed by first and last authors and a spread sheet was constructed including sample size, potential biases, and conclusions.Discussions regarding incorporation of available evidence into our clinical practice were held at biannual meetings, as well as through email and virtual meetings. An expert consensus was determined through these discussions and confirmed through a modified Delphi process.Extracorporeal life support in hematopoietic cell transplantation patients is being used with increasing frequency and potentially improving survival. The Pediatric Acute Lung Injury and Sepsis Investigators hematopoietic cell transplantation-cancer immunotherapy subgroup has developed a framework to guide physicians in decision-making surrounding extracorporeal life support candidacy in pediatric hematopoietic cell transplantation patients. In addition to standard extracorporeal life support considerations, candidacy in the hematopoietic cell transplantation population should consider the following six factors in order of consensus agreement: 1) patient comorbidities; 2) underlying disease necessitating hematopoietic cell transplantation; 3) hematopoietic cell transplantation toxicities, 4) family and patient desires for goals of care; 5) hematopoietic cell transplantation preparatory regimen; and 6) graft characteristics. Although risk assessment may be individualized, data are currently insufficient to clearly delineate ideal candidacy. Therefore, we urge the onco-critical care community to collaborate and capture data to provide better evidence to guide physicians' decision-making in the future.

This Good Practice Paper was compiled according to the British Society for Haematology (BSH) process at http://www.b-s-h.org.uk/guidelines. The BSH produces Good Practice Papers to recommend good practice in areas where there is a limited evidence base but for which a degree of consensus or uniformity is likely to be beneficial to patient care. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup.org and is also detailed in Table 1.

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species’ sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom—immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)—were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20–40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

Chronic lymphocytic leukemia (CLL) mainly affects older people: the median age at diagnosis is > 70 years. Elderly patients with CLL are heterogeneous with regard both to the biology of their disease and aging. Following the diagnosis of CLL in an elderly individual, careful risk assessment is essential when treatment options are evaluated. This includes not only clinical staging and evaluation of disease-specific prognostic biomarkers such as 17p deletion and TP53 mutation, but also of comorbidities, physical capacity, nutritional status, cognitive capacity, ability to perform activities of daily living and social support. Comorbidity scoring and geriatric assessment tools are helpful in achieving such multidimensional evaluation in a systematic manner. The introduction of new drugs including novel monoclonal antibodies and kinase inhibitors offers enhanced opportunities for the treatment of elderly patients with CLL. This position paper of a Task Force of the International Society of Geriatric Oncology (SIOG) reviews currently available evidence relevant to such patients. All types of elderly patient (i.e. chronological age > 65–70 years) are considered, from robust (fit) to vulnerable (unfit) to the terminally ill. Among the topics covered are the following: (i) the relationship between chronological age, prognosis and survival, (ii) assessment of biological aging, (iii) biological age as a determinant of treatment feasibility and tolerance and (iv) tailoring of both first and further-line treatment to the circumstances of the individual patient.

The therapy of advanced (clear-cell) renal cell carcinoma (RCC) has recently experienced tremendous changes. Several new treatments have been developed, with PD-1 immune-checkpoint inhibition being the backbone of therapy. Diverse immunotherapy combinations change current first-line standards. These changes also require new approaches in subsequent lines of therapy. In an expert panel, we discussed the new treatment options and how they change clinical practice. While first-line immunotherapies introduce a new level of response rates, data on second-line therapies remains poor. This scenario poses a challenge for clinicians as guideline recommendations are based on historical patient cohorts and agents may lack the appropriate label for their in guidelines recommended use. Here, we summarize relevant clinical data and consider appropriate treatment strategies.

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment.

Hepatocellular carcinoma (HCC) ranks number three among the most frequent causes of death from solid tumors worldwide. With obesity and fatty liver diseases as risk factors on the rise, HCC represents an ever increasing challenge. While there is still no curative treatment for most patients numerous novel drugs have been proposed, but most ultimately failed in phase III trials. This manuscript targets therapeutic advances and most burning issues. Expert key point summaries and urgent research agenda are provided regarding risk factors, including microbiota, need for prognostic and predictive biomarkers and the equivocal role of liver biopsy. Therapeutic topics highlighted are locoregional techniques, combination therapies and the potential of immunotherapy. Finally the manuscript provides a critical evaluation of novel targets and strategies for personalized treatment of HCC.

2-D : two-dimensional 3-D : three-dimensional 5-FU : 5-fluorouracil ACE : angiotensin-converting enzyme ARB : angiotensin II receptor blocker ASE : American Society of Echocardiography BNP : B-type natriuretic peptide CABG : coronary artery bypass graft CAD : coronary artery

Tyrosine kinase inhibitors still play a very important role in the treatment of metastatic renal cell carcinoma despite a continuously changing scenario, in which immunotherapy and several combination-based approaches are also available. In this light, patient-reported outcomes and health-related quality of life are important factors in the selection of the best first-line treatment. This Review focuses on the existing evidence on patient-reported outcomes and health-related quality of life with several tyrosine kinase inhibitors (pazopanib, sunitinib, cabozantinib and tivozanib) used as first-line treatment for metastatic renal cell carcinoma.

Contains fulltext : 202812.pdf (Publisher’s version ) (Open Access) A multitude of new agents for the treatment of hematologic malignancies has been introduced over the past decade. Hematologists, infectious disease specialists, stem cell transplant experts, pulmonologists and radiologists have met within the framework of the European Conference on Infections in Leukemia (ECIL) to provide a critical state-of-the-art on infectious complications associated with immunotherapeutic and molecular targeted agents used in clinical routine. For brentuximab vedotin, blinatumomab, CTLA4- and PD-1/PD-L1-inhibitors as well as for ibrutinib, idelalisib, HDAC inhibitors, mTOR inhibitors, ruxolitinib, and venetoclax, a detailed review of data available until August 2018 has been conducted, and specific recommendations for prophylaxis, diagnostic and differential diagnostic procedures as well as for clinical management have been developed.

Malignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined with the longer life expectancy, this led to an increasing prevalence of melanoma in the older population. Recently, immune checkpoint inhibitors significantly improved the treatment of melanoma given their efficacy and tolerability profile. Two major classes of agents include the anti-cytotoxic T lymphocyte-associated protein 4 (CFLA-4) inhibitors, such as ipilimumab, and the anti-programmed death-ligand 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab. Treatment of metastatic disease with immune checkpoint inhibitors demonstrated improved efficacy and better safety profiles compared to cytotoxic drugs and appears to be an attractive treatment option. Nevertheless, there is a need for tools designed to better predict which older patients will benefit from its use and who will experience toxicities related to the treatment. Current data do not show a major increase in toxicity rates in older patients. However, patients above 75 are often under-represented and those who are included are not representative of the general population of older patients, thereby also stressing the need for real-life data. Ongoing research is aiming at maximizing the potential treatment efficacy and developing novel immune-targeting modalities. Future studies should include older patients and assess geriatric domains in these older patients to better guide decision-making. This review discusses published clinical trials and where known, the efficacy and toxicity in older patients. Moreover, the clinical implications and future perspectives are discussed, with current recommendations for older patients, management of toxicities, and a proposal for an initial approach to the treatment of older patients with metastatic melanoma. (C) 2018 Elsevier Ltd. All rights reserved.

An autoimmune subset of chronic spontaneous urticaria is increasingly being recognized internationally, based on laboratory and clinical evidence that has accrued over the last 20 years. This evidence has been reviewed by a taskforce of the Dermatology section of the European Academy of Allergy and Clinical Immunology. Functional autoantibodies in chronic urticaria (CU) patient sera have been demonstrated against IgE and FcεRIα by basophil and mast cell histamine release assays and by basophil activation assays. Antibody specificity has been confirmed by immunoassay, but there is a poor correlation between functionality and immunoreactivity. Approximately 25% of CU patients have a positive basophil histamine release assay and show autoreactivity (a positive autologous serum skin test), whereas 50% are negative regarding both. Functionality of CU sera appears to be complement dependent on mast cells but not exclusively on basophils. Basophil activation by CU sera is predominantly restricted to IgG1 and IgG3 subclasses. Circumstantial evidence for CU being an autoimmune disease comes from an observed association with other autoimmune diseases, a strong association between serum functionality and HLA-DR4 haplotype and the good response of CU patients to immunotherapies. It was proposed that a study should be undertaken to prospectively validate potentially relevant clinical criteria (from the history, examination and routinely available clinical investigations) against a new 'gold standard' for the diagnosis of ACU (positive autoreactivity, functional bioassay and immunoassay) to define preliminary criteria sets for the diagnosis of ACU based on clinical and laboratory features with highest individual sensitivity and specificity.

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.

As the overall prevalence of asthma has escalated in the past decades, so has the population of patients with severe asthma. This condition is often difficult to manage due to the relative limitation of effective therapeutic options for the physician and the social and economic burden of the disease on the patient. Management should include an evaluation and elimination of modifiable risk factors such as smoking, allergen exposure, obesity and non-adherence, as well as therapy for co-morbidities like gastro-esophageal reflux disease and obstructive sleep apnea. Current treatment options include conventional agents such as inhalational corticosteroids, long acting β(2) agonists, leukotriene antagonists, and oral corticosteroids. Less conventional treatment options include immunotherapy with methotrexate, cyclosporine and tacrolimus, biological drugs like monoclonal antibodies, tumor necrosis factor-α blockers and oligonucleotides, phosphodiesterase inhibitors, antimicrobials and bronchial thermoplasty.

Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (∼10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy.

Adoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma. A number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival. Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates. These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma. Here, we provide an overview of the current state-of-the art in T-cell–based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field. Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone are described. Finally, we provide a roadmap describing the critical steps required to test TIL therapy in a randomized multicenter setting. We suggest an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency. If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer. Clin Cancer Res; 17(7); 1664–73. ©2011 AACR.