Diagnosis and initial treatment of transplant-eligible high-risk myeloma patients: A British Society for Haematology/UK Myeloma Society Good Practice Paper.

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.

Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper.

Multiple myeloma is a bone marrow-based plasma cell tumour that develops from asymptomatic pre-cursor conditions smouldering myeloma and monoclonal gammopathy of uncertain significance and all are characterised by the presence of a monoclonal protein in the blood. Diagnosis and distinction between these conditions is based on blood tests, the bone marrow biopsy and cross sectional imaging. There are various risk stratification models that group patients with smouldering myeloma into risk groups based on risk of progression to symptomatic disease. Management is mainly observational for patients with smouldering myeloma although clinical trials for high-risk disease may be available. Restaging is required if evidence for progression.

Advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma: A British Society of Haematology and UK Myeloma Society Good Practice Paper.

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.

Investigation and management of the monoclonal gammopathy of undetermined significance: A British Society for Haematology Good Practice Paper.

This Good Practice Paper provides recommendations for the diagnosis, risk stratification and management of the monoclonal gammopathy of undetermined significance (MGUS). It describes the recently recognised entity of the monoclonal gammopathy of clinical significance (MGCS), and recommends how it should be managed. The potential for targeted population screening for MGUS is also discussed.

Long term outcomes in monoclonal gammopathy of renal significance.

Unlike AL amyloid and cast nephropathy, the long-term outcomes of monoclonal gammopathy of renal significance (MGRS) patients with other renal histopathologies remain unclear. It is uncertain if early intervention improves renal outcomes, because of a lack of evidence from prospective studies. In this retrospective study, we examined outcomes of 41 MGRS patients treated between 2004 and 2017 across five centres: four in the UK and one in the Republic of Ireland. The primary outcome measure was renal survival estimated by Kaplan-Meier product-limit method. Thirty-three patients (80·5%) were kappa light chain (LC) restricted. Twenty-seven patients (65·9%) presented with LC deposition disease on renal histology. At 24 months follow-up, estimated renal survival was 81·6% for the whole cohort. The estimated overall survival was 80·3% at 48 months. At 24 months, patients who had chronic kidney disease (CKD) stage 2-3b at diagnosis showed an estimated renal survival of 100% compared to 80·7% in those with CKD stage 4-5 at diagnosis (P = 0·04). Poorer outcomes in MGRS patients were historically attributed to delayed diagnosis due to small plasma cell clones, as well as the need for renal biopsy.

Real-life experiences with omalizumab for the treatment of chronic urticaria.

BACKGROUND: Evidence has shown that omalizumab, a subcutaneous anti-IgE monoclonal antibody, is highly effective for the treatment of chronic urticaria. OBJECTIVE: To evaluate omalizumab 150 mg/month in severe, difficult-to-treat, chronic urticaria in a real-life setting. METHODS: This prospective open-label study evaluated of 150 mg of omalizumab in severe urticaria defined by a 7-day urticaria activity score (UAS-7) higher than 30, a history of oral glucocorticoid use, and by suboptimal response to previous treatments. Two subgroups of patients at different centers (Toronto and Quebec City, Canada) were included. The primary efficacy evaluation was a change in UAS-7 from baseline. A quantitative medication score assessed the use of other anti-urticarial medications. RESULTS: Sixty-eight patients were included: 61 with chronic spontaneous urticaria, 6 with cold urticaria, and 1 with urticarial vasculitis. Patients were followed for up to 25 months. In Toronto, mean UAS-7 decreased from 32.2 at baseline to 5.7 after the last omalizumab treatment. Seventy-nine percent achieved complete remission during omalizumab therapy (UAS-7 0) and 6 (18%) showed improvement but never achieved complete remission. The most common maintenance dosing intervals were 1 to 3 months. In Quebec City, from baseline to 18 months, mean UAS-7 decreased from 24.4 to 2.2 and the quantitative medication score decreased from 13.3 to 3.0. All 6 patients with cold urticaria became symptom free, with a significant decrease of their cold stimulation tolerance test. CONCLUSION: Omalizumab 150 mg was effective in difficult to treat patients with severe, chronic urticaria refractory to recommended treatments who usually required prednisone. Omalizumab induced a long-lasting positive response and was well tolerated without side effects.

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

Long-term efficacy of fixed-dose omalizumab for patients with severe chronic spontaneous urticaria.

BACKGROUND: Treatment of chronic urticaria is challenging because many patients are refractory to or experience adverse effects with conventional therapy. Recently, short-term efficacy of omalizumab has been demonstrated. OBJECTIVE: To determine both the short- and long-term efficacy of omalizumab in the treatment of chronic urticaria. METHODS: Sixteen patients with severe chronic spontaneous urticaria at our center received omalizumab, 150 mg every 2 to 4 weeks, between 2010 and 2011. Disease severity was measured by urticaria activity scores before the first injection, during treatment, and at most recent follow-up, ranging from 9 to 24 months. Duration of therapy was determined individually for each patient. In this retrospective analysis, outcome measures include number of treatments required to induce remission and long-term remission sustainability. RESULTS: Ten patients had remission of urticaria after their first injection (62%). Four patients required 2 to 6 treatments to achieve remission. Two patients discontinued treatment after 2 injections. Of the 14 patients who initially benefited (88%), 4 remain in remission more than 9 months after their last treatments. Seven patients continue to achieve remission with maintenance omalizumab, dosed at intervals appropriate for individual remission duration. Three patients became refractory and discontinued treatment (19%). CONCLUSION: Omalizumab is an effective treatment for inducing and maintaining long-term remission for patients with severe chronic urticaria. Onset of remission is rapid, although duration is variable, with some patients requiring maintenance treatment. Large-scale randomized trials are necessary to confirm our findings that support the long-term efficacy of anti-IgE therapy for the treatment of this disease.

An Economic Model to Establish the Costs Associated With Routes to Presentation for Patients With Multiple Myeloma in the United Kingdom.

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.

Presenting Symptoms in Newly Diagnosed Myeloma, Relation to Organ Damage, and Implications for Symptom-Directed Screening: A Secondary Analysis from the Tackling Early Morbidity and Mortality in Myeloma (TEAMM) Trial.

Multiple myeloma (MM) patients risk diagnostic delays and irreversible organ damage. In those with newly diagnosed myeloma, we explored the presenting symptoms to identify early signals of MM and their relationships to organ damage. The symptoms were recorded in patients' own words at diagnosis and included diagnostic time intervals. Those seen by a haematologist >6 months prior to MM diagnosis were classified as precursor disease (PD). Most (962/977) patients provided data. Back pain (38%), other pain (31%) and systemic symptoms (28%) predominated. Patients rarely complain of 'bone pain', simply 'pain'. Vertebral fractures are under-recognised as pathological and are the predominant irreversible organ damage (27% of patients), impacting the performance status (PS) and associated with back pain (odds ratio (OR) 6.14 [CI 4.47-8.44]), bone disease (OR 3.71 [CI 1.88-7.32]) and age >65 years (OR 1.58 [CI 1.15-2.17]). Renal failure is less frequent and associated with gastrointestinal symptoms (OR 2.23 [CI1.28-3.91]), age >65 years (OR 2.14 [CI1.28-3.91]) and absence of back pain (OR 0.44 [CI 0.29-0.67]). Patients with known PD (n = 149) had fewer vertebral fractures (p = 0.001), fewer adverse features (p = 0.001), less decline in PS (p = 0.001) and a lower stage (p = 0.04) than 813 with de novo MM. Our data suggest subgroups suitable for trials of 'symptom-directed' screening: those with back pain, unexplained pain, a general decline in health or low-impact vertebral compression fractures.

Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma.

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; P = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; P = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. Keywords: MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. Supplemental material is available for this article. © RSNA, 2021.

A trust approach for sharing research reagents.

The core feature of trusts-holding property for the benefit of others-is well suited to constructing a research community that treats reagents as public goods.