Search

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup conducted a workshop on Immune and Cellular Therapy in Multiple Myeloma on January 7, 2022. This workshop included presentations by basic, translational, and clinical researchers with expertise in plasma cell dyscrasias. Four main topics were discussed: platforms for myeloma disease evaluation, insights into pathophysiology, therapeutic target and resistance mechanisms, and cellular therapy for multiple myeloma. Here we provide a comprehensive summary of these workshop presentations.

Light chain measurements form an essential component of the testing strategy for the detection and monitoring of patients with suspected and/or proven plasma cell disorders. Urine-based electrophoretic assays remain at the centre of the international guidelines for response assessment but the supplementary role of serum-free light chain (FLC) assays in response assessment and the detection of disease progression due to their increased sensitivity has been increasingly recognised since their introduction in 2001. Serum FLC assays have also been shown to be prognostic across the spectrum of plasma cell disorders and are now incorporated into risk stratification scores for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma, and light chain amyloidosis (AL amyloidosis), as well as being incorporated into the criteria for defining symptomatic multiple myeloma. There are now multiple different commercially available serum FLC assays available with differing performance characteristics, which are discussed in this review, along with the implications of these for patient monitoring. Finally, newer methodologies for the identification and characterisation of monoclonal FLC, including modifications to electrophoretic techniques, mass spectrometry-based assays and Amylite, are also described along with the relevant published data available regarding the performance of each assay. [ABSTRACT FROM AUTHOR]

Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams. [ABSTRACT FROM AUTHOR]

Keywords: JAK2 inhibitors; multiple myeloma; myeloma immune; microenvironment EN JAK2 inhibitors multiple myeloma myeloma immune microenvironment 420 422 3 02/02/21 20210201 NES 210201 Ruxolitinib was the first Janus kinase (JAK) inhibitor approved by the United States Food and Drug Administration (FDA) in November 2011 for the treatment of myelofibrosis and was shortly followed by the approval of tofacitinib for the treatment of rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. If early phase trials with ruxolitinib show promise then questions will then arise as to whether other JAK2 inhibitors are more effective than ruxolitinib, the infection risk of combined therapies with JAK2 inhibitors in patients with relapsed myeloma and the optimal use of JAK2 inhibitors in terms of dosing and combinations. JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation. [Extracted from the article]

Introduction: Previous guidelines considered body mass index (BMI) over 40 kg/m 2 a relative contra-indication to liver transplantation (LT). The aims were to examine the selection process and study outcomes of patients with Class I-III obesity., Methods: Retrospective analysis of outcomes of obese patients assessed for LT at our center between 2010 and 2023, divided into three groups: Class I (BMI30-34.9 kg/m 2 ), Class II (BMI35-39.9 kg/m 2 ), and Class III (BMI>40 kg/m 2 ). Survival of non-obese adult patients was used for comparison., Results: Three hundred fifteen patients with BMI ≥30 kg/m 2 were assessed for LT. Seventeen (5.4%) were not wait-listed due to comorbidities. One hundred sixty-eight patients were transplanted: 100 Class I, 43 Class II, and 25 Class III. There were no differences in postoperative complications (Clavien-Dindo Grade 3 or more; 41%, 42%, 48% for Class I-III obesity respectively) or patient and graft survival (5-y rates 84.4% and 82.7%, respectively, for the whole cohort) according to the different classes of obesity. Furthermore, patient and graft survival was not different between non-obese and obese patients (p = 0.932)., Conclusion: With a rigorous selection process, short-term outcomes after LT for patients with Class III obesity were comparable to patients with Class I-II obesity. Long-term survival was identical for obese and non-obese patients., (© 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)