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This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

Kaiser et al. offer management recommendations for transplant‐eligible, high‐risk multiple myeloma (HRMM), derived from recent trials exploring treatment intensification in the various phases of front‐line therapy. The definition of HRMM continues to evolve with emergence of novel genomic insights and impact of modern therapies, underscoring the need to expand beyond traditional interphase fluorescence in situ hybridization cytogenetics and International Staging System staging for a precise risk assessment. Despite progress, ongoing challenges in treatment delivery and tolerability underscore the urgency for exploring novel approaches like T‐cell redirecting bispecific antibodies and chimeric antigen receptor T‐cell to enhance outcomes in this complex patient population.Commentary on: Kaiser et al. Diagnosis and initial treatment of transplant‐eligible high‐risk myeloma patients: A British Society for Haematology/UK Myeloma Society Good Practice Paper. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19623 [ABSTRACT FROM AUTHOR]

Recent clinical studies demonstrated the achievement of lymphoma responses in patients with Hepatitis C virus‐associated indolent lymphoproliferative disorders (LPD) receiving direct‐acting antivirals (DAAs) as their sole treatment. However, the molecular mechanisms underlying LPD responses to DAAs are still poorly understood. In their paper the authors provide new molecular insights on this issue, reporting intraclonal diversification and persistence of B‐cell clones in most cases, despite viral eradication and beneficial clinical outcome. These provocative data suggest that the achievement of molecular response is probably not required for a 'functional cure' of these patients. Further comprehensive immunogenetic and mutational studies would be fundamental to dissect this biological puzzle and, ultimately, to refine improved treatment strategies in this setting. Commentary on: Mazzaro et al. Persistence of monoclonal B‐cell expansion and intraclonal diversification despite virus eradication in patients affected by hepatitis C virus‐associated lymphoproliferative disorders. Br J Haematol 2023;203:237‐243. [ABSTRACT FROM AUTHOR]

Observation is recommended for patients without immunoglobulin M (IgM)-related complications and/or symptoms related to bone marrow or extramedullary lymphoplasmacytic involvement.2 Asymptomatic IgM monoclonal gammopathy encompasses two clinicopathological entities with a distinct risk of progression to symptomatic WM: IgM monoclonal gammopathy of undetermined significance (IgM MGUS) and smouldering WM (SWM). In their paper, Zanwar I et al i .11 focussed on patients with SWM with the aim of identifying risk factors for early progression to symptomatic WM. Interestingly, they were able to identify a subset of patients (30% of patients with the two variables available) with a high risk of progression to symptomatic WM (median TTP 2-4 years). Zanwar I et al i .11 report that patients with SWM represent one-fifth of patients with WM. [Extracted from the article]

Mass cytometry in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome: looking for a needle in a haystack In their current paper, Kourelis I et al i . profile the different immune cells within the bone marrow (BM) of patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) (Kourelis I et al. i , [8]). Different immune checkpoint regulators are expressed by HRS cells, but PD-L1 is found to be universally present on HRS cells due to a genetic amplification at chromosome 9 (De Goycoechea I et al. i , [6]). [Extracted from the article]

In this seminal paper, Dr. Kyle pointed out how some, but not all, MGUS patients would develop a plasmacytoid or lymphoproliferative disorder over time, suggesting that the nature of MGUS was undetermined, rather than benign. Prior to this definition, most MGRS patients would have been diagnosed as having MGUS and therefore not deemed eligible for treatment. In a recent retrospective study from the Medical University of Innsbruck, Austria, of over 2900 patients diagnosed with MGUS between 2000 and 2016, only 44 patients (1-5%) were diagnosed with MGRS. [Extracted from the article]

Among the B-cell lymphoproliferative disorders, monoclonal gammopathy of undetermined significance (MGUS) is the humoral counterpart to monoclonal B-cell lymphocytosis. This review introduces the papers from the section devoted to MGUS at the International Workshop entitled ‘Monoclonal B-cell lymphocytosis and chronic lymphocytic leukaemia: environmental and genetic risk factors.’ [ABSTRACT FROM AUTHOR]