MADRID, IPIC2019 CONGRESS REPORT 6-8 NOVEMBER 2019 HIGHLIGHT REPORT event IPOPI an DIAGNOSIS AND CLINICAL CARE 6-8 NOVEMBER MADRID, SPAIN CONGRESS REPORT FOCUS ON DIAGNOSIS AND CLINICAL CARE 1 IPIC2019 CONGRESS REPORT MADRID, HIGHLIGHT REPORT 6-8 NOVEMBER 2019 2 INTERNATIONAL PRIMARY IMMUNODEFICIENCIES CONGRESS - IPIC2019 MADRID, IPIC2019 CONGRESS REPORT 6-8 NOVEMBER 2019 HIGHLIGHT REPORT FOCUS ON DIAGNOSIS AND CLINICAL CARE 3 CONGRESS ORGANISERS IPIC2019 CONGRESS REPORT MADRID, HIGHLIGHT REPORT 6-8 NOVEMBER 2019 INTERNATIONAL PATIENT ORGANISATION FOR PRIMARY IMMUNODEFICIENCIES ABOUT IPOPI IPOPI (International Patient Organisation for Primary Immunodeficiencies) is the leading advocate for primary immunodefi- ciencies’ (PIDs) patients worldwide. We work in collaboration with patients, doctors, politicians, regulators, pharmaceutical industry and other relevant stakeholders. IPOPI is the Association of national patient organisations and our work is dedicated to improving awareness, access to early diagnosis and optimal treatments for primary immunodeficiencies’ patients worldwide through global collaboration. IPOPI has an increasing membership and currently represents 68 National Member Organisations spread across all continents. IPOPI is an international charity registered in the United Kingdom and under UK Charity Law. STRATEGIC PLAN 2016-2020 Our activities are carried out with a strategy-driven approach and geared towards the 4 following strategic objectives: 1 - To promote early diagnosis & ensure optimal access to care 2 - To develop, strengthen and support National Member Organisations (NMOs) 3 - To raise PID awareness globally 4 - To stimulate stakeholder collaboration FIND US ONLINE The best way to learn about IPOPI and our activities and achievements is through our website www.ipopi.org. You will find all our statements, events, members’ contacts, the IPOPI PID Map, etc. e-News, our quarterly electronic newsletter, is our main periodic communications’ tool. It is released each year in March, June, September and December and features three specific sections: IPOPI’s News, Around the world and NMO Focus. Read more: e-News.ipopi.org Watch TV.IPOPI.org to find all IPOPI’s video contents including patient testimonials, physician interviews and clinical manage- ment lectures on primary immunodeficiencies. The videos have been sorted around dedicated sections on Access to care, Diag- nosis, Quality of life and Clinical Management. IPOPI is active on Facebook, Twitter, and LinkedIn and we look forward to meeting you there as well! www.linkedin.com/company/international-patient-organisation-for-primary-immunodefiency tv.ipopi.org twitter/ipopi_info facebook.com/ipopipid ipopi.org 4 INTERNATIONAL PRIMARY IMMUNODEFICIENCIES CONGRESS - IPIC2019 SUPPORTING ORGANISATIONS IPIC2019 CONGRESS REPORT MADRID, 6-8 NOVEMBER 2019 SUPPORTING ORGANISATIONS FOCUS ON DIAGNOSIS AND CLINICAL CARE 5 IPIC2019 CONGRESS REPORT MADRID, EXECUTIVE SUMMARY 6-8 NOVEMBER 2019 IPIC2019 CONGRESS REPORT (by Dr Lizzy Rivers*) IPIC2019, the 4th IPOPI International Primary Immunodeficiencies Congress (IPIC), held in Madrid, Spain, saw the joining of 750 clinicians, scientists, patient support and advocacy groups from 70 countries, bringing science and clinical care to- gether with the aim of improving care for patients with primary immunodeficiencies (PIDs). The programme celebrated the incredible work carried out by our global PID network but also highlighted work still needing to be done. Here, a summary is presented of the conference main sessions, where updates in knowledge of disease as well as advances in supportive and definitive therapies for PIDs were discussed. * Dr Lizzy Rivers is a member of the IPOPI Medical Advisory Panel and works at Great Ormond Street Hospital for Children in London. IPOPI wishes to sincerely thank her for the preparation of this congress report. KEY MESSAGES: • Understanding the molecular basis of disease remains key to progressing the field of PID diagnosis and treatments • Advances in diagnostics bring challenges in evaluation of novel variants of uncertain significance • Important information on side effects and the potential monitoring needed for novel therapies is emerging but with limited follow-up so far - collaboration is needed to share experiences • The value of parents and patient organisations in policy making cannot be underestimated 6 INTERNATIONAL PRIMARY IMMUNODEFICIENCIES CONGRESS - IPIC2019 IPIC2019 CONGRESS REPORT MADRID, 6-8 NOVEMBER 2019 TABLE OF CONTENTS DAY 1: WEDNESDAY 6TH NOVEMBER 2019 Welcome Session: Pushing the boundaries of PIDs towards new horizons 8 DAY 2: THURSDAY 7TH NOVEMBER 2019 Opening session 10 Session 1: Management of Respiratory issues in PID 10 Session 2: PID testing and screening – a look at novel PID diagnostics 12 Session 3: The Good, the Bad and the Ugly: Management of complex PID cases 14 Session 4: Regional clinical priorities 16 DAY 3: FRIDAY 8TH NOVEMBER 2019 Session 5: PID management ethical considerations 20 Session 6: Latest treatment advances in immune dysregulation 21 Session 7: 20 years of gene therapy – the past and future 22 Session 8: Diagnosing and treating PIDs in adulthood and old age 25 Closing Session: PID diagnosis and care – where will we be in 10 years from now? 27 Abbreviations 28 Abstracts approved for Poster Presentation 32 Congress Sponsors 250 FOCUS ON DIAGNOSIS AND CLINICAL CARE 7 IPIC2019 CONGRESS REPORT MADRID, DAY 1: WEDNESDAY 6TH NOVEMBER 2019 6-8 NOVEMBER 2019 WELCOME SESSION: PUSHING THE BOUNDARIES OF PIDs TOWARDS NEW HORIZONS • Functional evaluation of novel variants is essential in determining their significance • In addition to detecting new inborn errors of immunity, whole genome sequencing is also identifying PID mimics • With the discovery of targeted therapies for immune dysregulation, we are learning the delicate balance of managing immunosuppression with susceptibility to infection • Collaboration across disciplines is essential in sharing ideas and understanding for the advancement of PIDs and their mimics • The ‘PID classification’ app is a great resource for trainees and experts alike Prof Stuart Tangye, Chair of the IUIS committee, opened the Welcome Session with a useful update on IUIS classifi- cation and highlighted how exploration of the molecular causes of PIDs has done so much for assisting management of patients and medicine beyond PID. This was demonstrated eloquently using the example of XLA. Since its discovery in 1952, dramatic improvement of patients on immunoglobulin (Ig) replacement led to extension of use of Ig to successfully protect other PID patients. It was not for another 40+ years that the BTK gene was found to be the cause of absent B cell development, exploitation of which has now been successfully adapted for treatment of B cell lymphoma using BTK inhibitors. With the advent of next generation sequencing (NGS), there has been a huge increase in rates of gene discovery for inborn errors of immunity (latest 430 PID genes). This brings its own problems of when to call a variant “pathogenic”, with much work needed in functional evaluation and correlation with clinical phenotypes. The committee has a huge task in classifying variants based on their clinical and immunological phenotype. Possible diagnoses can be browsed by pre- dominant immunophenotypes or alternatively, specific clinical and/ or immunophenotypic features can be entered into the search category to return potential diagnoses. Dr Anne Puel echoed the importance of functional evaluation of novel variants, particularly in determining whether they are predicted to cause loss or gain of function effects. She shared her experience of the drug ruxolitinib (member of the family of JAK (Janus kinase) inhibitors) for STAT 1 gain of function (GOF) patients where, prior to its use at her centre, haematopoietic stem cell transplantation (HSCT) in 15 patients was associated with only 40% overall survival (OS) and significant risk of graft failure. Following its introduction in 2015, ruxolitinib seems to be a game changer with reports of significant improvement in patient symptoms. However, caution was raised about its use in those with invasive fungal disease prior to JAK inhibition, which appears to be associated with significant morbidity and mortality. Dr Puel’s experi- ence of 11 patients on ruxolitinib (dose 0.4 to 2mg/kg/day or 15mg/m2 BD) found improvement in cytopaenias, interstitial lung disease and enteropathy. Nonetheless, one patient died from disseminated coccidiomycosis. There also appears to be a significant risk of viral reactivation with CMV, EBV, BKV, JCV, VZV and prophylaxis with aciclovir is recommended. ESID President, Prof Isabelle Meyts, concluded the session by reminding about the importance of considering PID mim- ics in the management of undefined PIDs. Barrier functions of epithelia play important roles in host defence, with defects resulting in recurrent infections that may phenocopy PID. This was illustrated with two case presentations, the diagnoses of which only came to light after whole genome sequencing; the first, a patient presenting as hyper IgE syndrome (HIES) that turned out to have a variant in a gap junction gene (GJA1) and the second, a patient presenting with an IPEX-like phe- notype who was found to have SAM syndrome (Severe dermatitis, multiple Allergies and Metabolic wasting). Conversely, Cystic fibrosis (CF), traditionally considered a PID mimic, has been a condition of particular interest in recent years, with evidence