Diagnosis and management of monoclonal gammopathy of renal significance: A British Society for Haematology good practice paper.

This guideline provides consensus opinion on the investigations required for people presenting with suspected monoclonal gammopathy of renal significance to both nephrology and haematology physicians. The guideline discusses the principles of treating a patient with MGRS and provides recommendations for both supportive management and haematological therapy. It details the recommended on-going monitoring required for both specialty areas.

Recurrent Fibrillary Glomerulonephritis Secondary to Chronic Lymphocytic Leukemia: Remission of Kidney Disease with Ibrutinib.

Introduction: Fibrillary glomerulonephritis (FGN) is a rare form of glomerular disease that accounts for less than 1 percent of all renal biopsies. It is characterized by pathognomonic electron microscopy findings of fibrillar deposits in the mesangium and glomerular capillary walls. FGN was initially considered to be an idiopathic disorder.

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.

PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's Macroglobulinaemia.

The optimal therapeutic approach for relapsed/refractory (R/R) Waldenström's Macroglobulinaemia (WM) has not been clearly defined, especially after treatment with chemoimmunotherapy (CIT) and covalent Bruton's tyrosine kinase inhibitors (cBTKi). The PembroWM trial is a multi-centre, phase II, single-arm study assessing the safety, tolerability and efficacy of rituximab with pembrolizumab in R/R WM patients who had received at least one prior line of treatment, with all having relapsed post-CIT and most also exposed to cBTKi. A total of 17 patients were enrolled, with a median age of 70, and median of three prior lines of therapy with 15 either refractory or intolerant of a cBTKi.

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.

National myeloma patient survey shows continuing inappropriate imaging and geographical inequalities.

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.

The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival.

T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of the immune system. Approximately 20% of pediatric and 50% of adult T-ALL patients have refractory disease or relapse and die from the disease. To improve patient outcome new therapeutics are needed.

Long-term outcomes by bone marrow B-cell depletion from the R2W trial of bortezomib with cyclophosphamide and rituximab in Waldenstrőm macroglobulinaemia.

There remains a lack of consensus as to the most appropriate primary therapy in Waldenstrőm macroglobulinemia (WM). We evaluated a novel bortezomib-based combination and developed a sensitive WM-specific flow cytometry assay (limit of detection 0.004% of leucocytes) to assess bone marrow (BM) response.

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.

Image quality in whole-body MRI using the MY-RADS protocol in a prospective multi-centre multiple myeloma study.

Background: The Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines establish a standardised acquisition and analysis pipeline for whole-body MRI (WB-MRI) in patients with myeloma. This is the first study to assess image quality in a multi-centre prospective trial using MY-RADS.

Methods: The cohort consisted of 121 examinations acquired across ten sites with a range of prior WB-MRI experience, three scanner manufacturers and two field strengths.

SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.

SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1 cells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction.

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.

Uptake of long-chain fatty acids from the bone marrow suppresses CD8+ T-cell metabolism and function in multiple myeloma.

T cells demonstrate impaired function in multiple myeloma (MM) but suppressive mechanisms in the bone marrow microenvironment remain poorly defined. We observe that bone marrow CD8+ T-cell function is decreased in MM compared with controls, and is also consistently lower within bone marrow samples than in matched peripheral blood samples. These changes are accompanied by decreased mitochondrial mass and markedly elevated long-chain fatty acid uptake.

Delayed diagnosis resulting in increased disease burden in multiple myeloma: the legacy of the COVID-19 pandemic.

The COVID-19 pandemic has had global healthcare impacts, including high mortality from SARS-CoV-2 infection in cancer patients; individuals with multiple myeloma (MM) are especially susceptible to poor outcomes. However, even for MM patients who avoided severe infection, the ramifications of the pandemic have been considerable. The consequences of necessary socio-geographical behavior adaptation, including prolonged shielding and interruptions in delivery of non-pandemic medical services are yet to be fully understood.

Benefits of switching from intravenous to subcutaneous daratumumab: Perspectives from UK healthcare providers.

Daratumumab is a CD38-directed monoclonal antibody indicated to treat multiple myeloma (MM). Daratumumab was initially administered intravenously (IV), subsequently a subcutaneous (SC) formulation was developed to increase convenience of administration. The UK was an early adopter of SC daratumumab and, as such, this report provides consensus recommendations from a group of UK MM experts, with the aim of facilitating the transition from IV to SC daratumumab for other European healthcare providers.

Immune responses to COVID-19 booster vaccinations in intensively anti-CD38 antibody treated patients with ultra-high-risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial.

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.