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Indigenous hepatitis E is increasingly recognized in developed countries, where it may be a zoonosis. We describe the first case of transfusion-transmitted hepatitis E in the UK from a blood donor who had no history of recent travel abroad. Follow-up of the donor and recipients of the blood products was carried out using serological and molecular techniques. Acute hepatitis E was transmitted to one of two recipients. The infected patient would have received a larger volume of the donor's plasma. HEV subgenomic sequences carried by the donor and recipient were identical. This is the first case of post-transfusion hepatitis E in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic country may occur by blood transfusion. It is important that blood donors inform the transfusion service of all post-donation illnesses so that appropriate interventions can take place. [ABSTRACT FROM AUTHOR]

This Good Practice Paper provides recommendations for the use of advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma. It describes how advanced imaging contributes to optimal healthcare resource utilisation by in newly diagnosed and relapsed myeloma, and provides a perspective on future directions of myeloma imaging, including machine learning assisted reporting., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

This Good Practice Paper provides recommendations for the diagnosis and initial management of transplant-eligible high-risk myeloma patients. It describes recent updates to the genetic diagnostics of high-risk myeloma and provides recommendations for treatment on the basis of recent prospective clinical trial evidence., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To evaluate the provision of imaging at diagnosis of myeloma from the service user perspective with a specific focus on how the experiences of patients align with the National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) on first-line imaging practice for myeloma in the United Kingdom., Methods: A national survey was performed to evaluate access to imaging from the patient's perspective. Patients with myeloma who received their diagnosis between 2017 and March 2022 were invited to participate. Data were collected using an online survey from 895 patients and carers between 4 and 14 March 2022., Results: Most patients had more than one imaging test. First-line MRI was used in 69.2% of respondents. First-line skeletal survey (SS, whole body X-rays) remained common (48.7% of respondents). 18F-fluorodexyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was used least often (23.1% of respondents). SS was used more often in East England (57.9%) and Scotland (61.2%) than in South East England (36.3%)., Conclusions: Despite NICE recommendations, first-line MRI was not used in a third of patients surveyed, with geographical variation in imaging practice. Patients are still undergoing multiple imaging tests at diagnosis. Healthcare professionals should continue to emphasize the superiority of MRI compared to SS to drive for improvements in care., Advances in Knowledge: Current recommendations on first-line imaging for myeloma are not provided consistently across the United Kingdom. There is a need to drive change and support healthcare professionals to deliver guidance-based recommendations to improve experience and outcomes for patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Multiple myeloma (MM) and anti-MM therapy cause profound immunosuppression, leaving patients vulnerable to coronavirus disease 2019 (COVID-19) and other infections. We investigated anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies longitudinally in ultra-high-risk patients with MM receiving risk-adapted, intensive anti-CD38 combined therapy in the Myeloma UK (MUK) nine trial. Despite continuous intensive therapy, seroconversion was achieved in all patients, but required a greater number of vaccinations compared to healthy individuals, highlighting the importance of booster vaccinations in this population. Reassuringly, high antibody cross-reactivity was found with current variants of concern, prior to Omicron subvariant adapted boostering. Multiple booster vaccine doses can provide effective protection from COVID-19, even with intensive anti-CD38 therapy for high-risk MM., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Patients with myeloma often face significant diagnostic delay, with up to one-third of UK patients diagnosed after an emergency presentation (EP). Compared with other routes, patients presenting as an emergency have more advanced disease, increased complications, and poorer prognosis., Methods: An economic model was developed using a decision-tree framework and lifetime time horizon to estimate costs related to different presentation routes (EP, general practitioner [GP] 2-week wait, GP urgent, GP routine, and consultant to consultant) for UK patients diagnosed as having myeloma. After diagnosis, patients received one of 3 first-line management options (observation, active treatment, or end-of-life care). Inputs were derived from UK health technology assessments and targeted literature reviews, or based on authors' clinical experience where data were unavailable. Active treatment, complication, and end-of-life care costs were included., Results: The average per-patient cost of treating myeloma (across all routes) was estimated at £146 261. The average per-patient cost associated with EP (£152 677) was the highest; differences were minimal compared with GP 2-week wait (£149 631) and consultant to consultant (£147 237). GP urgent (£140 025) and GP routine (£130 212) were associated with marginally lower costs. Complication (£42 252) and end-of-life care (£11 273) costs were numerically higher for EP than other routes (£25 021-£38 170 and £9772-£10 458, respectively)., Conclusions: An economic benefit may be associated with earlier diagnosis, gained via reduced complication and end-of-life care costs. Strategies to expedite myeloma diagnosis and minimize EPs have the potential to improve patient outcomes and may result in long-term savings that could offset any upfront costs associated with their implementation., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12-20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15-25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Multiple myeloma is a plasma cell malignancy that accounts for 1%-2% of newly diagnosed cancers.At diagnosis, approximately 20% of patients can be identified, using cytogenetics, to have inferior survival (high-risk). Additionally, standard-risk patients, with detectable disease (minimal residual disease (MRD)-positive) postautologus stem cell transplant (ASCT), fare worse compared with those who do not (MRD-negative). Research is required to determine whether a risk-adapted approach post-ASCT could further improve patient outcomes., Methods: RADAR is a UK, multicentre, risk-adapted, response-guided, open-label, randomised controlled trial for transplant-eligible newly diagnosed multiple myeloma patients, using combinations of lenalidomide (R), cyclophosphamide (Cy), bortezomib (Bor), dexamethasone (D) and isatuximab (Isa).Participants receive RCyBorD(x4) induction therapy, followed by high-dose melphalan and ASCT. Post-ASCT, there are three pathways as follows:A phase III discontinuation design to assess de-escalating therapy in standard-risk MRD-negative patients. Participants receive 12 cycles of Isa maintenance. Those who remain MRD-negative are randomised to either continue or stop treatment.A phase II/III multiarm multistage design to test treatment strategies for treatment escalation in standard-risk MRD-positive patients. Participants are randomised to either; R, RBorD(x4) +R, RIsa, or RBorIsaD(x4) + RIsa.A phase II design to assess the activity of intensive treatment strategies in high-risk patients. Participants are randomised to RBorD(x4) +R or RBorIsaD(x4) + RIsa.1400 participants will be registered to allow for 500, 450 and 172 participants in each pathway. Randomisations are equal and treatment is given until disease progression or intolerance., Ethics and Dissemination: Ethical approval was granted by the London-Central Research Ethics Committee (20/LO/0238) and capacity and capability confirmed by the appropriate local research and development department for each participating centre prior to opening recruitment. Participant informed consent is required before trial registration and reconfirmed post-ASCT. Results will be disseminated by conference presentations and peer-reviewed publications., Trial Registration Number: ISCRTN46841867., Competing Interests: Competing interests: ABC, KLR, DAC, AH, CO, LBai, LBar, AP and RL report grants and non-financial support from BMS/Celgene, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Amgen, grants and non-financial support from Takeda, during the conduct of the trial. DAC also reports travel support from Celgene Corporation. KY, RDT, CB, GJ, GP, MC, BD, DM, GC, HA, KR,SA and AC have no conflicting interests to declare. MC declares, Bristol Myers Squibb- employee, Honoraria/travel support in the last 3 years from, Amgen, BMS/Celgene, Janssen, Takeda, Abbvie. CP declares BMS/Celgene Ad boards and speaker fees, Sanotif—Ad board, speaker fees, conference registration fees. JS reports Carrying out consultancy work (Advisory Board) for Sanofi. And an educational speaking engagement for Celgene/BMS RP declares; Honoraria—Jannsen, BMS, Abbvie, GSK. Consultancy: GSK, Janssen. Meeting support: Janssen, Takeda, BMS. RO declares- Janssen - advisory board, honoraria, Celegene— honoraria, Beigene - advisory board, honoraria, Astra Zeneca—honoraria. MK declares inter-relationships: AbbVie: consultancy; Amgen: honoraria; BMS/Celgene: consultancy, research funding (institution); GSK: consultancy; Janssen: consultancy, research funding (institution); Karyopharm: consultancy; Pfizer: consultancy; SeattleGenetics: consultancy; Takeda: consultancy; Sanofi: honoraria. MD reports owning stock in Abingdon Health. SQ is the founder and CSO of Achilles therapeutics a company developing T cell therapies for solid tumours., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Depth of response is the critical determinant of prognosis in amyloid light-chain (AL) amyloidosis. Here, we aim to identify patients who are unlikely to improve response based on analysis of baseline characteristics and 1-month response. In a multivariate model, difference in involved amyloidogenic and uninvolved serum free light chains (dFLC) at diagnosis (dFLC >400 mg/l, odds ratio [OR] 4.051, p < 0.005) and no response at 1 month (OR 4.787, p < 0.005) were significant predictors of no improvement in response. Only 5% of patients with a dFLC of >400 mg/l and no response at 1 month improved their response (p < 0.005). We suggest that these patients should switch treatment early, subject to their functional status., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)

Aims: To evaluate current national imaging practice in myeloma with reference to National Institute for Health and Care Excellence (NICE) guidelines (NG35, 2016) and compare results with an initial survey conducted in 2017 (61 participating sites)., Materials and Methods: All UK radiology departments treating myeloma patients and with a Royal College of Radiologists (RCR) Audit Lead were invited to participate. Data were collected using an online questionnaire. Descriptive statistics were performed., Results: One hundred and fourteen hospitals supplied data (54% return rate). Skeletal survey (SS) remains the most-commonly performed first-line imaging test for suspected/confirmed myeloma or plasmacytoma (39%, 45/114 hospitals), followed by whole-body magnetic resonance imaging (WBMRI) (27%, 31/114) and whole-body computed tomography (WBCT) (19%, 22/114). Integrated positron-emission tomography/CT (PET/CT) was first-line in 14% (16/114). The NICE recommended initial investigation, WBMRI, is currently offered in 27% of surveyed hospitals (<10% in 2017). Ongoing challenges to implementing WBMRI include scanner availability, financial constraints, reporting time, and radiologist training., Conclusion: Despite NICE recommendations regarding WBMRI in diagnosis/follow-up of myeloma, SS (poor sensitivity and specificity) remains the most commonly performed first-line test. Radiologists, haematologists, and patients should continue to emphasise the superiority and benefit of modern and more accurate imaging, such that they are prioritised in clinical service planning., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Renal injury is a common complication of multiple myeloma (MM) and is associated with adverse outcome. Despite this, the natural history of renal injury in patients with MM remains uncertain especially in the context of intensive therapy and novel therapies. To address the lack of data, we evaluated the renal function of 2334 patients from the UK National Cancer Research Institute Myeloma XI trial at baseline and at 12 months to assess renal function over time and the factors associated with change. Patients who had severe acute kidney injury or a requirement for dialysis were excluded. At 12 months of the 1450 evaluable patients planned for autologous transplantation; 204 (14%) patients had a decline in estimated glomerular filtration rate (eGFR) ≥25% from baseline, 341 (23.5%) had an improvement and 905 (62%) had no significant change in eGFR. Renal outcome at 12 months for the 884 evaluable patients who were not planned for transplant was similar. Improved renal function was more likely if patients were <70 years old, male, had an average eGFR <60 mL per minute per 1.73 m2 and a higher baseline free light chain level >1000 mg/L, and/or a free light chain response of >90%. It did not correlate with monoclonal-protein response, transplantation, or use of a bortezomib-based regimen. We show that with current therapies the proportion of patients who have a significant decline in renal function in the first 12 months is small. The greatest relative improvement in eGFR is seen in patients with high free light chain at baseline and a high light chain response. This trial was registered at http://www.isrctn.com as #49407852., (© 2020 by The American Society of Hematology.)