Abstract: To compare patients with primary immune thrombocytopenia (ITP) prescribed early (within 3 months of initial ITP treatment) second-line treatment (eltrombopag, romiplostim, rituximab, immunosuppressive agents, splenectomy) with or without concomitant first-line therapy to those who received only first-line therapy. This real-world retrospective cohort study of 8268 patients with primary ITP from a large US-based database (Optum ®  de-identified Electronic Health Record [EHR] dataset) combined electronic claims and EHR data. Outcomes included platelet count, bleeding events, and corticosteroid exposure 3 to 6 months after initial treatment. Baseline platelet counts were lower in patients receiving early second-line therapy (10‒28 × 10 9 /L) versus those who did not (67 × 10 9 /L). Counts improved and bleeding events decreased from baseline in all treatment groups 3 to 6 months after the start of therapy. Among the very few patients for whom follow-up treatment data were available ( n  = 94), corticosteroid use was reduced during the 3- to 6-month follow-up period in patients who received early second-line therapy versus those who did not (39% vs 87%, p   〈  0.001). Early second-line treatment was prescribed for more severe cases of ITP and appeared to be associated with improved platelet counts and bleeding outcomes 3 to 6 months after initial therapy. Early second-line therapy also appeared to reduce corticosteroid use after 3 months, although the small number of patients with follow-up data on treatment precludes any substantive conclusions. Further research is needed to determine whether early second-line therapy has an effect on the long-term course of ITP.

Abstract: Background Tyrosine kinase inhibitors (TKIs) are the standard of care for patients (pts) with CML-CP. The current recommendation is to continue TKI therapy indefinitely.1 Results of several clinical trials indicate that pts achieving sustainable deep molecular response (DMR; defined as molecular response ≥ MR4) on imatinib (IM) may achieve long-lasting TFR. Nilotinib (NIL) at 300 mg bid induces higher rates of DMRs compared to IM.2 Also, DMRs can be achieved in pts with NIL (400 mg bid) who are switched after long-term IM.3 However, the optimal duration of consolidation treatment with NIL to increase the chances for successful and continuous TFR (≥ MR4) after stopping treatment is not yet known. Objective ENESTPath was designed to assess the proportion of pts (pretreated with IM and subsequently treated with NIL 300 mg bid) who can achieve a sustained DMR and maintain TFR without relapse for 12 months (mo) upon treatment discontinuation after different durations of treatment in consolidation phase. Methods ENESTPath is a randomized, phase 3 study enrolling pts with CML-CP who achieved a complete cytogenetic response (CCyR), but not MR4, after at least 24 mo of treatment with IM. After enrollment, pts were assigned to receive NIL at 300 mg bid for either 24 mo or 36 mo (arm 1 and arm 2, respectively). Pts with stable MR4 or better for at least 12 mo will enter the TFR phase. A stable MR4 was defined by 4 of the 5 preceding quarterly real-time quantitative RT-PCR (RQ-PCR) assessments ≥ MR4 and ≥ MR4 inthe last assessment performed by IS certified EUTOS laboratories. Results A total of 619 pts were enrolled in the study between May 2013 and June 2015. The present analysis reports the results of the first 300 pts (mean age, 50.8 years; 63.7% of males) enrolled and treated with NIL for 24 mo in induction and consolidation phase or who had discontinued earlier. Details of the baseline characteristics are given in Table 1. At data cutoff, 108 pts were in stable MR4; 101 (33.7%) were randomized and 7 (2.3%) were scheduled for randomization at that time point. 192 pts (64%) were not eligible for randomization, primarily due to lack of stable MR4 in 126 pts (42%), adverse events (AEs) or abnormal laboratory values in 44 pts (14.7%), and for other reasons in 22 pts (7.3%). The rates of MR4 at baseline*, 6 mo, 12 mo, 18 mo, and 24 mo were 14.3%, 43.3%, 45.7%, 43.7%, and 46%, respectively. By 24 mo of treatment with NIL, cumulative incidences of major molecular response (MMR), MR4, and MR4.5 of all treated pts not in respective MR at baseline were 93.2%, 69.3% and 42.1%, respectively (Figure 1). Further analysis showed that pts with MMR at baseline had a higher probability of achieving an MR4 than those lacking MMR at baseline, with a cumulative incidence of MR4 by 24 mo of 75.8% and 44.2%, respectively. No new safety signals were observed during the 24 mo consolidation with NIL. The majority of the AEs were low grade. Most common AEs irrespective of the relationship to the study drug were pruritus (19%), hypercholesterolemia (14.0%), rash (10.7%), asthenia (10%), and arthralgia (10%). The most common newly occurring or worsening all-grade biochemistry laboratory abnormalities included increase in total cholesterol (68.7%), increased ALT (54%), hyperglycemia (32.7%), and hyperbilirubinemia (37%); majority of them were grade 1 and 2. Newly occurring or worsening all-grade cytopenias include anemia (12.7%), thrombocytopenia (2.3%), leukopenia (2%), and neutropenia (1%). Grade 3 or 4 cardiovascular events (CVEs) were experienced by 6.7% of pts including ischemic heart disease (4.7%), peripheral artery occlusive disease (1.7%), and ischemic cerebrovascular events (0.7%) (Table 2). Conclusions This analysis of the first 300 pts after 24 mo of NIL treatment showed a cumulative incidence of MR4 in ~ 70% of pts who were not in MR4 at baseline with an advantage in favor of MMR at baseline. 108 pts (36%) were with stable MR4 at data cutoff and 192 pts (64%) discontinued the study due to very stringent protocol definitions of eligibility for randomization and AEs. Grade 3 or 4 AEs were consistent with the previous reports.4 References 1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Myelogenous Leukemia V.1.2016 ©2016 National Comprehensive Cancer Network, Inc. 2. Hochhaus A, et al. Leukemia. 2016;30:1044-1054. 3. Hughes TP, et al. Blood. 2014;124:729-736. 4. Rea D, et al. Blood. 2015;125:[abstract 4040]. Disclosures Rea: Ariad: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Rosti:Roche: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Incyte: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Cross:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Niederwieser:Novartis: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau. Pregno:Novartis: Honoraria; BMS: Honoraria; ARIAD: Honoraria. Orlandi:Ariad: Honoraria; BMS: Honoraria; Novartis: Honoraria. Almeida:Celgene: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Shire: Speakers Bureau; Alexion: Speakers Bureau. Illes:University of Debrecen faculty of medicine department of hematology: Employment. Sagues:ICO-Girona/hospital Universtiari de Girona Dr. Josep Trueta: Employment. Haenig:Novartis: Employment. Supekar:Novartis: Employment. Shah:Cognizant: Employment; Novartis: Other: Vendor. Saglio:Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Steegmann:Aria: Honoraria, Other: Research funding for Spanish CML Group; BMS: Honoraria, Other: Research funding for Spanish CML Group; Novartis: Honoraria, Other: Research funding for Spanish CML Group; Pfizer: Honoraria, Other: Research funding for Spanish CML Group. Baccarani:Pfizer: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau.

Abstract: Corticosteriods (CSs) remain the standard of care for immune thrombocytopenia (ITP); however, many patients relapse after initial treatment, and long-term CS use is associated with considerable toxicity and tolerability issues (Provan et al. Blood 2010). Clinically, there is a need for a less toxic regimen that will provide sustained response. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) currently approved in the United States for the treatment of ITP in patients who have had an insufficient response to CSs, immunoglobulins, or splenectomy. Limited evidence from retrospective studies and the phase II ESTIT study (NCT02402998) suggests that earlier use of TPO-RAs after ITP diagnosis may allow a larger proportion of patients to achieve sustained responses after tapering off drug (Červinek et al. Int J Hematol 2015; Gonzalez-Lopez et al. Am J Hematol 2015; Newland et al. Br J Haematol 2016; Lucchini, et al. Haematologica 2019). TAPER (NCT03524612) is an ongoing phase II, open-label, prospective, single-arm study assessing sustained response off treatment in adult patients with ITP receiving eltrombopag, who had relapsed or failed to respond to initial CS treatment. Eligible patients are adults (≥ 18 years old) with ITP who are not responsive to or are in relapse after first-line CS therapy ± immunoglobulins used as rescue therapy, with platelet counts & lt; 30×109/L, and assessed as needing treatment. Patients receive a starting dose of 50 mg eltrombopag QD (East/Southeast Asian ancestry: 25 mg QD; Japanese patients treated in Japan: 12.5 mg QD per approved starting dose in the Japanese prescribing information). The primary endpoint is the number (%) of patients with sustained responses off treatment by Month 12. Sustained response is defined as a complete response (platelet count ≥ 100×109/L) with platelet counts ≥ 70×109/L maintained for 2 months, followed by dose reduction and treatment discontinuation while maintaining platelet counts ≥ 30×109/L, without bleeding or rescue therapy, until Month 12. Platelet counts are assessed weekly during the first 8 weeks of treatment, and biweekly thereafter, depending on patient response. Rescue therapy is permitted within the first 14 days of study treatment and does not preclude patients from reaching the primary endpoint criteria, if successful discontinuation of eltrombopag is reached and maintained at Month 12. The proportion of patients who reach the primary endpoint will be summarized with the 95% confidence interval (Clopper-Pearson method). A binomial test for one proportion, H0: P = 0.15 vs. H1: P & gt; 0.15 will be performed to test if the proportion of remission patients is greater than 15%, using a target alpha level of 0.05. Patients who meet the primary endpoint at 12 months will be followed up for an additional 12 months.Patients who relapse between Months 12 and 24 will be offered retreatment with eltrombopag until the end of Month 24. Secondary endpoints will include measures of quality of life, and exploratory endpoints will include biomarker assessments of immunomodulation. Here, we report an update on trial recruitment and patient baseline characteristic data from an early data cut (November 15, 2019). An estimated 101 patients across 50 sites will be enrolled; 47 sites are currently active and 3 are pending site initiation visits. As of November 15, 2019, 66 patients had been screened, 53 of whom had been enrolled and had undergone treatment. Of the patients enrolled, 60.4% were female and the mean (± standard deviation) age was 49.4 (± 19.0) years. The majority of patients were White (88.7%). On June 24, 2020, patients from 15 countries worldwide were committed to screening (Figure 1); the number of patients screened had risen to 98, with 82 patients enrolled. The planned study timeline has been disrupted due to the COVID-19 pandemic. Enrollment is expected to complete in November 2020, with final results expected in 2023. Conclusion: The purpose of this trial is to assess sustained response off treatment following eltrombopag therapy in patients with ITP who failed to respond to or have relapsed after initial treatment with steroids. The data generated by TAPER will provide insights into whether eltrombopag could be a viable treatment option after first-line steroid treatment. If this were confirmed, the earlier use of eltrombopag could have the potential to reduce the toxicity from repeated steroid exposure in patients with ITP. Disclosures Cooper: Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Ghanima:Amgen: Honoraria, Speakers Bureau; Bristol Myers Squibb: Research Funding; Bayer: Research Funding; Novartis: Honoraria, Speakers Bureau; Principia: Honoraria, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau. Haenig:Novartis: Current Employment. Lee:Novartis: Current Employment, Other: Novartis AG equity holder. Rahman:Novartis: Other: Full time employee of IQVIA which provides services to Novartis; IQVIA: Current Employment. Zaja:Kyowa Kirin: Honoraria, Speakers Bureau; Mundipharma: Honoraria, Speakers Bureau; Novartis: Honoraria, Patents & Royalties: Pending patent (No. PAT058521) relating to TAPER trial (NCT03524612), Speakers Bureau; Roche: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Grifols: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen-Cilag: Honoraria, Speakers Bureau.

Abstract: Tyrosine kinase inhibitor (TKI) trough plasma level testing and pharmacodynamic evaluation (i.e. quantification of phosphorylated BCR-ABL downstream targets) may help to optimize patient-tailored dosing in CML-CP. For 2nd generation TKIs the clinical value of TKI plasma level and protein phosphorylation quantification remains unclear. The ENEST1st study (NCT01061177) is focused on examining the role of first-line nilotinib therapy in CML-CP. This ENEST1st substudy addresses the value of plasma-level testing and protein single cell phosphorylation pharmacodynamics as predictors of response and long-term outcomes. Methods Nilotinib levels were centrally quantified by means of mass spectrometry (HPLC-MS/MS) in 54 patients at 3 hours after first drug intake at day (d) 1 (Cmax) and at d7, d28 as well as at months (mo) 3, 6, 12 prior to morning drug intake (Cmin=trough level). Single cell quantification of intracellular protein phosphorylation was performed by flow cytometry (phosphoflow) in the myelocyte cell population after full blood fixation/cell permeabilization/erythrocyte lysis and analyzed 3 hours after first drug intake at d1 and on d7 and d28. Primary endpoint of the study was MR4 (BCR-ABL 〈 0.01% IS) at 18 months. Results Our initial analysis focuses on correlation of drug levels with molecular response by correlating PK data to early molecular response, i.e. ≤10% BCR-ABL (IS) reduction at 3 mo as well as 0.1% IS (MMR), MR4 and MR5. At 3, 6, 12 and 18 mo, 24%, 56%, 74% and 77 % of the here investigated patients achieved MMR; 2%, 22%, 34% and 44% achieved MR4 and MR5 was detected in 0%, 5%, 15% and 14% of patients at the respective time points. Only 1 patient at 3mo had 〉 IS 10% BCR-ABL. On d1 at 3 hours after intake of the first tablet the median peak plasma levels reached 408 ng/ml increasing to a median trough level of 834 ng/ml at d7, 888 ng/ml at d28, 919 ng/ml at 3mo, 1122 ng/ml at 6m and 1003 ng/ml at 12mo. Initial Cmax-levels at d1 significantly correlated with steady state levels thereafter (e.g. with trough levels at 12mo: r=0.56, p=0.004). Three mo drug levels were significantly negatively associated with lower BCR-ABL mRNA burden at 12m and 24m (r=-0.44, p=0.011 for m12 and r=-0.35, p=0.014 for m24). When median steady state drug levels were compared in different response categories (yes/no: MR4, MR5, MMR, 〉 IS 10% at 3mo), significantly higher nilotinib trough levels at day 90 and mean trough level (day 28-180) were seen in patients achieving the primary endpoint of the study (MR4 at 18mo). Similarly, 3mo and mean through levels were also significantly higher in patients achieving MR5 at 12 or 18mo. As only one patient did not reach 〈 10% at 3mo, we cannot evaluate if early PK data are able to predict this endpoint. The probability of achieving MR5 at 12mo and 24mo was significantly higher in the top third of the day 90 PK level (cumulative incidence of MR5 in the respective PK groups at 12mo: 5.6% vs. 5.6% vs. 44.4% and at 24mo: 5.6% vs. 22% vs. 44.4%). Cumulative incidence of MR4 was faster in the higher PK group (6mo: 6% vs. 18% vs. 42%; 12mo: 22% vs. 29% vs. 57% and at 24mo: 46% vs. 67% vs. 58%), which however did not reach statistical significance. Phosphoflow of myelocytes revealed that compared to baseline, phosphorylation of almost all investigated proteins decreases over time, including significant reduction of phospho-Gab2(Y452), Abl(Y245), STAT5(Y694), Erk1/2(T202/Y204), and p38(T108/Y182) at d28. Correlation of plasma levels with changes in phosphorylation status revealed a negative correlation of increasing drug levels with decreasing phospho-p38 and phospho-STAT5 status. A more detailed signaling analysis of cellular subsets related to molecular response criteria are in progress. Conclusions Single cell myelocyte phosphoprotein detection allowed monitoring of the BCR-ABL signalling network. Inter-individual plasma levels show a relatively wide variability and Cmax levels upon first drug exposure correlate with later trough levels pointing out to a potential individual pharmacogenetic background regulating drug availability. PK-based optimizing of nilotinib-dosing may help to further improve response depth (i.e. reaching MR4 or MR5), which is assumed to be a prerequisite for treatment discontinuation. Disclosures: Wolf: Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Mustjoki:Novartis: Honoraria, Research Funding. Greil:Novartis: Honoraria, Research Funding. Hjorth-Hansen:Pfizer, BMS: Honoraria, Travel expenses Other. Verhoef:Novartis: Research Funding. Mark:Novartis: Employment. Haenig:Novartis: Employment. Jurjonas:Novartis: Employment. Giles:Novartis: Consultancy, Research Funding. Hochhaus:Novartis: Research Funding. Porkka:Novartis: Honoraria, Research Funding. Ossenkoppele:Novartis: Consultancy, Research Funding; BMS: Consultancy. Gjertsen:Novartis: Honoraria, Research Funding.

Abstract: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder defined by a platelet count & lt; 100 × 109/L without explanation, and an increased risk of bleeding. ITP itself as well as its treatments have multifaceted, often poorly understood impacts on patients' quality of life (QoL). These effects include impact on activities of daily living, emotional health, energy, ability to think well and clearly, and productivity in the workplace. There are limited data on which individual aspects of ITP are perceived both by patients and physicians as having the greatest impact on QoL. Understanding patients' perspectives is vital to optimize their QoL by specifying particular areas in need of therapy. I-WISh 1.0 was an exploratory, cross-sectional survey in which 1507 patients with ITP and 472 physicians across 13 countries completed separate, but related, online surveys that included assessments of ITP signs and symptoms, impact of symptoms, and patient-physician relationships. These findings have been presented at previous ASH and EHA congresses, and manuscripts are currently in preparation. However, although I-WISh 1.0 provided considerable insights into unexplored facets of the effects of ITP, an all-too-large number of gaps in understanding still remain. In response to this, I-WISh 2.0 is currently being developed. The objectives of the I-WISh 2.0 patient and physician cross-sectional surveys include: (1) to further explore the burden of fatigue and how it affects patients' lives, including what makes it better or worse; (2) to assess the emotional impact of living with chronic ITP, especially in relation to depression; (3) to assess how treatments for ITP can impact activities of daily living (positively and negatively); (4) to further relate effects of treatment to patients' QoL; and (5) to explore how telemedicine affects healthcare delivery for patients with ITP. Furthermore, data from subsets of patients will address (6) the impact of COVID-19 in patients with ITP; and (7) special issues affecting ITP in pregnancy. A steering committee of ITP expert physicians and patient advocacy group representatives are designing and will endorse the patient and physician surveys now nearing readiness after several meetings to determine the areas of greatest need of assessment. In addition, a control group will be included. Survey launch and data collection are scheduled to commence in early Q4 2020. Patients and physicians will complete similar online surveys. Both patient and physician surveys include a screener and sections of questions related to the specific objectives of I-WISh 2.0. The surveys include updates to key topics in I-WISh 1.0 (impact of fatigue, impact on daily life, treatment of ITP, emotional impact of ITP); validated patient-reported outcome tools to measure fatigue (MFIS-5), presence and severity of depression (PHQ-9), work-related burden (WPAI), and impact on quality of life (ILQI) tools; and questions related to COVID-19, telemedicine (remote patient monitoring), and pregnancy and ITP. Patients will be recruited to I-WISh 2.0 via treating physicians and patient advocacy groups, and will be included if they are ≥ 18 years of age, diagnosed with ITP, and agree to participate. Participating physicians will be required to be actively managing patients with ITP and have a minimum caseload of 3 ITP patients currently under their care; physicians must also have a primary specialty of hematology or hematology-oncology. Approval will be sought from an independent centralized Institutional Review Board. Data analysis will be primarily descriptive and correlative in nature. Breakdown by country and geographic areas will be included. A global sample is planned from 21 countries across 6 continents, with the aim of surveying more than 2000 patients and 600 physicians. I-WISh 2.0 will be the largest observational global survey ever conducted in ITP. If accepted, preliminary data are planned to be presented at the ASH meeting. I-WISh 2.0 will build on the strengths of I-WISh 1.0, which highlighted areas requiring further assessment and will explore aspects of ITP of great interest that were neither conclusively addressed in the first survey nor well-studied in the past. Disclosures Ghanima: Bristol Myers Squibb:Research Funding;Principia:Honoraria, Speakers Bureau;Pfizer:Honoraria, Research Funding, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;Novartis:Honoraria, Speakers Bureau;Bayer:Research Funding.Provan:ONO Pharmaceutical:Consultancy;MedImmune:Consultancy;UCB:Consultancy;Amgen:Honoraria, Research Funding;Novartis:Honoraria, Research Funding.Cooper:Amgen:Honoraria, Speakers Bureau;Novartis:Honoraria, Speakers Bureau.Matzdorff:Roche Pharma AG:Other: Family stockownership;Amgen GmbH:Consultancy, Other: Honoraria paid to institution;Grifols Deutschland GmbH:Consultancy, Other: Honoraria paid to institution;Swedish Orphan Biovitrium GmbH:Consultancy, Other: Honoraria paid to institution;UCB Biopharma SRL:Consultancy, Other: Honoraria paid to institution;Novartis Oncology:Consultancy, Other: Honoraria paid to institution.Santoro:Novartis:Honoraria, Speakers Bureau;Takeda:Honoraria, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;Novo Nordisk:Honoraria, Speakers Bureau;Bayer:Honoraria, Speakers Bureau;CSL Behring:Honoraria, Speakers Bureau;Roche:Honoraria, Speakers Bureau;Sobi:Honoraria, Speakers Bureau.Morgan:Sobi:Other: Consultancy fees paid to the ITP Support Association;UCB:Other: Consultancy fees paid to the ITP Support Association;Novartis:Other: Consultancy fees paid to the ITP Support Association.Kruse:Principia:Other: Grant paid to PDSA;Pfizer:Other: Grant and consultancy fee, all paid to PDSA;Argenx:Other: Grant paid to PDSA;Novartis:Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work;CSL Behring:Other: Grant paid to PDSA;UCB:Other: Grant and consultancy fee, all paid to PDSA;Rigel:Other: Grant paid to PDSA;Amgen:Other: Grant and honorarium, all paid to PDSA.Zaja:Janssen-Cilag:Honoraria, Speakers Bureau;Takeda:Honoraria, Speakers Bureau;Bristol Myers Squibb:Honoraria, Speakers Bureau;Grifols:Honoraria, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;AbbVie:Honoraria, Speakers Bureau;Kyowa Kirin:Honoraria, Speakers Bureau;Mundipharma:Honoraria, Speakers Bureau;Novartis:Honoraria, Patents & Royalties: Pending patent (No. PAT058521) relating to TAPER trial (NCT03524612), Speakers Bureau;Roche:Honoraria, Speakers Bureau.Lahav:Novartis:Other: Consultancy fees paid to the Israeli ITP Support Association.Tomiyama:Novartis:Consultancy, Honoraria;Kyowa Kirin:Honoraria;Sysmex:Consultancy.Winograd:Novartis:Other: Consultancy fees paid to the Israeli ITP Support Association.Lovrencic:UCB:Other: Consultancy fees paid to AIPIT;Novartis:Other: Honorarium paid to AIPIT.Bailey:Adelphi Real World:Current Employment;Novartis:Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis.Haenig:Novartis:Current Employment.Bussel:Novartis:Consultancy;Argenx:Consultancy;UCB:Consultancy;CSL Behring:Consultancy;Shionogi:Consultancy;Regeneron:Consultancy;3SBios:Consultancy;Dova:Consultancy;Principia:Consultancy;Rigel:Consultancy;Momenta:Consultancy;RallyBio:Consultancy;Amgen:Consultancy.