Smouldering multiple myeloma: To seek or not to seek? To treat or not to treat. That is the question.

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence-based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193-1206.

Evaluating early intervention in smoldering myeloma clinical trials: a systematic review.

BACKGROUND: Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM. METHODS: All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life. RESULTS: Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively). CONCLUSION: In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

White matter paramagnetic rim and non-rim lesions share a periventricular gradient in multiple sclerosis: A 7-T imaging study.

BACKGROUND: Paramagnetic rim white matter (WM) lesions (PRL) are thought to be a main driver of non-relapsing multiple sclerosis (MS) progression. It is unknown whether cerebrospinal fluid (CSF)-soluble factors diffusing from the ventricles contribute to PRL formation. OBJECTIVE: To investigate the distribution of PRL and non-rim brain WM lesions as a function of distance from ventricular CSF, their relationship with cortical lesions, the contribution of lesion phenotype, and localization to neurological disability. METHODS: Lesion count and volume of PRL, non-rim WM, leukocortical lesion (LCL), and subpial/intracortical lesions were obtained at 7-T. The brain WM was divided into 1-mm-thick concentric rings radiating from the ventricles to extract PRL and non-rim WM lesion volume from each ring. RESULTS: In total, 61 MS patients with ⩾1 PRL were included in the study. Both PRL and non-rim WM lesion volumes were the highest in the periventricular WM and declined with increasing distance from ventricles. A CSF distance-independent association was found between non-rim WM lesions, PRL, and LCL, but not subpial/intracortical lesions. Periventricular non-rim WM lesion volume was the strongest predictor of neurological disability. CONCLUSIONS: Non-rim and PRL share a gradient of distribution from the ventricles toward the cortex, suggesting that CSF proximity equally impacts the prevalence of both lesion phenotypes.

Quantifying the Light-Absorption Properties and Molecular Composition of Brown Carbon Aerosol from Sub-Saharan African Biomass Combustion.

Sub-Saharan Africa is a hotspot for biomass burning (BB)-derived carbonaceous aerosols, including light-absorbing organic (brown) carbon (BrC). However, the chemically complex nature of BrC in BB aerosols from this region is not fully understood. We generated smoke in a chamber through smoldering combustion of common sub-Saharan African biomass fuels (hardwoods, cow dung, savanna grass, and leaves). We quantified aethalometer-based, real-time light-absorption properties of BrC-containing organic-rich BB aerosols, accounting for variations in wavelength, fuel type, relative humidity, and photochemical aging conditions. In filter samples collected from the chamber and Botswana in the winter, we identified 182 BrC species, classified into lignin pyrolysis products, nitroaromatics, coumarins, stilbenes, and flavonoids. Using an extensive set of standards, we determined species-specific mass and emission factors. Our analysis revealed a linear relationship between the combined BrC species contribution to chamber-measured BB aerosol mass (0.4-14%) and the mass-absorption cross-section at 370 nm (0.2-2.2 m2 g-1). Hierarchical clustering resolved key molecular-level components from the BrC matrix, with photochemically aged emissions from leaf and cow-dung burning showing BrC fingerprints similar to those found in Botswana aerosols. These quantitative findings could potentially help refine climate model predictions, aid in source apportionment, and inform effective air quality management policies for human health and the global climate.

How to Identify and Manage High-Risk Smoldering Multiple Myeloma.

PURPOSE OF REVIEW: It elucidates advancements in identifying and managing high-risk smoldering multiple myeloma (SMM), moving from observation strategies to intervention approaches. It highlights the significance of differentiating high-risk SMM from its less aggressive counterparts to prevent progression to multiple myeloma (MM). RECENT FINDINGS: Recent developments have improved SMM risk-stratification, integrating clinical, molecular and biological markers to identify high-risk individuals accurately. The advent of dynamic risk models that incorporate disease evolution and the application of novel diagnostic technologies are enhancing the understanding of SMM. Clinical trials exploring low to high intensity interventions, have shown promise in delaying MM onset and improving patient prognosis. There is a significant change in high-risk SMM management, leaning towards early intervention and precision medicine. The focus now is on refining these approaches, exploring new treatments, and proving the sustained benefits of early interventions to ultimately improve SMM patient care and outcomes.

Acquired von Willebrand Syndrome Associated with a Smoldering Multiple Myeloma, Successfully Treated by Daratumumab, Lenalidomide, and Dexamethasone.

INTRODUCTION: Acquired von Willebrand syndrome (AvWS) is a rare entity with approximately 700 cases described in the literature. A number of etiologies are responsible for this condition, mainly lymphoproliferative, myeloproliferative syndromes and cardiac diseases. Management is aimed at preventing and treating bleeds, as well as treating the underlying pathology. In the case of a monoclonal gammopathy, there are limited evidence and high heterogeneity only based on old case reports, resulting in poor quality recommendations. It seems essential in 2023 to take into account and offer the new anti-myeloma treatments available. CASE PRESENTATION: We describe the case of a patient with an AvWS secondary to an IgG smoldering multiple myeloma, experiencing multiple bleeding, treated successfully with daratumumab, lenalidomide, and dexamethasone, after multiple treatment failure. CONCLUSION: Daratumumab, lenalidomide, and dexamethasone was demonstrated as a rapid and effective treatment for a patient with severe AvWS and multiple bleeding complications.

Feasibility and solidification mechanism study of self-sustaining smoldering remediation for copper and lead-contaminated soil.

Soil heavy metal pollution is an important issue that affects human health and ecological well-being. In-situ thermal treatment techniques, such as self-sustaining smoldering combustion (SSS), have been widely studied for the treatment of organic pollutants. However, the lack of fuel in heavy metal-contaminated soil has hindered its application. In this study, we used corn straw as fuel to investigate the feasibility of SSS remediation for copper and lead in heavy metal-contaminated soil, as well as to explore the remediation mechanism. The results of the study showed that SSS increased soil pH, electrical conductivity (EC), total phosphorus (TP), total potassium (TK), rapidly available phosphorus (AP), and available potassium (AK), while decreasing total nitrogen (TN), alkali-hydrolyzed nitrogen (AN), and cation exchange capacity (CEC). The oxidation state of copper (Cu) increased from 10% to 21%-40%, and the residual state of lead (Pb) increased from 18% to 51%-73%. The Toxicity characteristic leaching procedure (TCLP) of Cu decreased by a maximum of 81.08%, and the extracted state of Diethylenetriaminepentaacetic acid (DTPA) decreased by 67.63%; the TCLP of Pb decreased by a maximum of 81.87%, and DTPA decreased by a maximum of 85.68%. The study indicates that SSS using corn straw as fuel successfully achieved remediation of heavy metal-contaminated soil. However, SSS does not reduce the content of copper and lead; it only changes their forms in the soil. The main reasons for the fixation of copper and lead during the SSS process are the adsorption of biochar, complexation with -OH functional groups, binding with π electrons, and the formation of crystalline compounds. This research provides a reference for the application of SSS in heavy metal-contaminated soil and has potential practical implications.

How do we image patients with multiple myeloma and precursor states?

Advances in morphological and functional imaging have led to superior detection of early bone disease, bone marrow infiltration, paramedullary and extramedullary involvement in multiple myeloma. The two functional imaging modalities that are most widely used and standardized are 18F-fluorodeoxyglucose-Positron emission tomography/computed tomography (FDG PET/CT) and whole-body magnetic resonance imaging with diffusion-weighted imaging (WB DW-MRI). Both prospective and retrospective studies have demonstrated that WB DW-MRI is more sensitive than PET/CT in the detection of baseline tumour burden and to assess response after therapy. In patients with smouldering multiple myeloma, WB DW-MRI is now the preferred imaging modality to rule out two or more unequivocal lesions which would be considered a myeloma-defining event by the updated international myeloma working group (IMWG) criteria. In addition to sensitive detection of baseline tumour burden, both PET/CT and WB DW-MRI have been successfully used for monitoring response to therapy and provide information that is complementary to IMWG response assessment and bone marrow minimal residual disease. In this article, we present 3 vignettes illustrating how we approach the use of modern imaging in the management of patients with multiple myeloma and precursor states, with a specific focus on recent data that have emerged since the publication of the IMWG consensus guideline on imaging. We have utilized data from prospective and retrospective studies to provide a rationale for our approach to imaging in these clinical scenarios and highlighted knowledge gaps requiring future investigation.

Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome.

Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers and with the presence of a specific bone marrow cell microenvironment (including increased MM cell infiltration). Finally, we verified by bioinformatic approaches in large transcriptomic and single cell datasets that a gene expression signature associated with ferritin biosynthesis correlated with worse outcome, MM cell proliferation, and specific immune cell profiles. Overall, we provide evidence of the role of ferritin as a predictive/prognostic factor in MM, setting the stage for future translational studies investigating ferritin and iron chelation as new targets for improving MM patient outcome.

Smouldering Myeloma: Chasing a Hyperviscous Sample.

Serum hyperviscosity is a rare laboratory finding. Amongst several causes of serum hyperviscosity, malignant disorders are quite common. Monoclonal gammopathy is a family of disorders in which monoclonal gammopathy of unknown significance (MGUS) and smoldering myeloma are the asymptomatic variants whereas multiple myeloma is the malignant variant showing different signs and symptoms related to bone lesions, renal failure and anemia. Initially during sample preparation, pipetting of a serum sample was found to be cumbersome. This sample during routine analysis in the automated analyser flagged repeated alarms for clot detection indicating a possibility of a hyper viscous sample. Serum was subjected to fibrinogen and D- dimer test. The D-Dimer levels were found to be normal and fibrinogen levels were mildly elevated. Routine biochemistry investigations were normal except grossly reversed A/G ratio. Due to gross reversal of A/G ratio, the possibility of Multiple myeloma was entertained. Physician's were alerted on telephone. Serum was sent for electrophoresis which showeda M spike. Bone marrow aspirate showed 13% plasma cells. Considering the above lab results the diagnosis of monoclonal gammopathy of smoldering type was considered. The sample was traced to a 77 years old male, who presented to Medicine OPD with the chief complaints of generalised weakness for two months without any history of fever. On physical examination pallor was evident but there was no icterus, cyanosis, clubbing, lymphadenopathy or edema. On haematological evaluation patient was found to be anemic. Careful tracking of hyperviscous patient's serum followed up by thorough investigation led us to the final conclusion that the case mentioned is a rare case of Smoldering type of multiple myeloma.

The evolution of immune dysfunction in multiple myeloma.

OBJECTIVES: This review discusses the role of immune dysfunction at the different stages of multiple myeloma (MM). METHODS: Narrative review. RESULTS: MM is a complex disease and immune dysfunction has been known to play an important role in disease pathogenesis, progression, and drug resistance. MM is known to be preceded by asymptomatic precursor states and progression from the precursor states to MM is likely related to a progressive impairment of the immune system. CONCLUSIONS: An understanding of the role of the immune system in the progression of MM is important to guide the development of immunotherapeutic strategies for this disease.

Prevalence and Clinical Characteristics of Paraproteinemia Associated with Chronic Myeloid Leukemia.

INTRODUCTION: Data regarding the prevalence of paraproteinemia in patients with chronic myeloid leukemia (CML) are lacking. METHODS: To evaluate for the prevalence of paraproteinemia, we undertook this cross-sectional study among consecutive chronic-phase CML patients. Complete blood count, chemistry, immunoglobulins, serum-free light chains, serum-protein electrophoresis and immunofixation were collected. Further analyses evaluated whether various patient-, disease-, and treatment-related variables are associated with paraproteinemia. RESULTS: One hundred patients, median age 63.5 (IQR 48.1-72) years were recruited. Median time from CML diagnosis to enrollment was 6.3 (IQR 2.3-11.3) years. Monoclonal protein was detected in 8 patients (8%), diagnosed with smoldering multiple myeloma (SMM, n = 2) and low-risk monoclonal gammopathy of undetermined significance (MGUS, n = 6). Six patients were on tyrosine kinase inhibitor treatment, 2 were in treatment-free remission. The only covariate associated with paraproteinemia was the presence of anemia, albeit with borderline statistical significance in univariate analysis (p = 0.053) and when adjusted for age (p = 0.056). CONCLUSIONS: In this largest study so far describing the prevalence of paraproteinemia among CML patients, we found MGUS prevalence to be higher than the 3.2% expected prevalence in the general population above 50 years and a non-negligible prevalence of SMM (2%). Screening for paraproteinemia in CML patients, especially in the presence of anemia, should be considered.

Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI.

Recent data suggest that multiple sclerosis white matter lesions surrounded by a rim of iron containing microglia, termed iron rim lesions, signify patients with more severe disease course and a propensity to develop progressive multiple sclerosis. So far, however, little is known regarding the dynamics of iron rim lesions over long-time follow-up. In a prospective longitudinal cohort study in 33 patients (17 females; 30 relapsing-remitting, three secondary progressive multiple sclerosis; median age 36.6 years (18.6-62.6), we characterized the evolution of iron rim lesions by MRI at 7 T with annual scanning. The longest follow-up was 7 years in a subgroup of eight patients. Median and mean observation period were 1 (0-7) and 2.9 (±2.6) years, respectively. Images were acquired using a fluid-attenuated inversion recovery sequence fused with iron-sensitive MRI phase data, termed FLAIR-SWI, as well as a magnetization prepared two rapid acquisition gradient echoes, termed MP2RAGE. Volumes and T1 relaxation times of lesions with and without iron rims were assessed by manual segmentation. The pathological substrates of periplaque signal changes outside the iron rims were corroborated by targeted histological analysis on 17 post-mortem cases (10 females; two relapsing-remitting, 13 secondary progressive and two primary progressive multiple sclerosis; median age 66 years (34-88), four of them with available post-mortem 7 T MRI data. We observed 16 nascent iron rim lesions, which mainly formed in relapsing-remitting multiple sclerosis. Iron rim lesion fraction was significantly higher in relapsing-remitting than progressive disease (17.8 versus 7.2%; P < 0.001). In secondary progressive multiple sclerosis only, iron rim lesions showed significantly different volume dynamics (P < 0.034) compared with non-rim lesions, which significantly shrank with time in both relapsing-remitting (P < 0.001) and secondary progressive multiple sclerosis (P < 0.004). The iron rims themselves gradually diminished with time (P < 0.008). Compared with relapsing-remitting multiple sclerosis, iron rim lesions in secondary progressive multiple sclerosis were significantly more destructive than non-iron rim lesions (P < 0.001), reflected by prolonged lesional T1 relaxation times and by progressively increasing changes ascribed to secondary axonal degeneration in the periplaque white matter. Our study for the first time shows that chronic active lesions in multiple sclerosis patients evolve over many years after their initial formation. The dynamics of iron rim lesions thus provide one explanation for progressive brain damage and disability accrual in patients. Their systematic recording might become useful as a tool for predicting disease progression and monitoring treatment in progressive multiple sclerosis.

Contrasting resistance of polycyclic aromatic hydrocarbons to atmospheric oxidation influenced by burning conditions.

The oxidation of polycyclic aromatic hydrocarbons (PAHs) determines their lifetime, toxicity and consequent environmental and climate impacts. The residential solid fuel burning composes of a substantial fraction of PAH emissions; however, their oxidation rate is yet to be explicitly understood, which is complicated by the contrasting emission factors under different combustion conditions and their subsequent evolution in the atmosphere. Here we used a plume evolution chamber using ambient oxidants to simulate the evolution of residential solid fuel burning emissions under real-world solar radiation, and then to investigate the oxidation process of the emitted PAHs. Contrasting oxidation rate of PAHs was found to be influenced by particles with or without presence of substantial amount of black carbon (BC). In the flaming burning phase, which contained 46% of BC mass fraction and 8% of organic aerosol (OA) internally mixed with BC, the larger PAHs (with 4-7 rings) was rapidly oxidized 12% for every hour of evolution under solar radiation; however, the larger PAHs from smoldering phase tended to maintain unmodified during the evolution, when 95% of OA was externally mixed with only minor fraction of BC (<5%). This may be ascribed to the complex morphology of BC, allowing more exposure for the internally-mixed OA to the oxidants; in contrast with those externally-mixed OA which was prone to be coated by condensed secondary substances. This raises an important consideration about the particle mixing state in influencing the oxidation of PAHs, particularly the coating on PAHs which may extend their lifetime and environmental impacts.

Exploring PCDD/Fs and potentially toxic elements in sewage sludge during smouldering treatment.

Potentially toxic elements (PTEs), persistent organic pollutants, and emerging contaminants make sewage sludge management challenging. There is significant interest in thermal treatment technologies that can destroy these compounds. The most common thermal treatment, incineration, poses risks due to formation and/or release of hazardous substances in process emissions such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and PTEs. Smouldering has been introduced recently as a potential treatment for managing sewage sludge. Smouldering systems present several advantages over traditional incinerators; however, there are still uncertainties regarding process by-products. This key question was investigated in three laboratory-scale tests (0.08 m radius) and five oil drum-scale tests (0.3 m radius) that were evaluated for PCDD/Fs and PTEs in the mixture before and after treatment as well as in process emissions. Volatile organic compounds (VOCs) were also measured. These experiments represent a broad spectrum of conditions to evaluate process emissions, from robust self-sustaining to extinction of smouldering. Robust smouldering had negligible PCDD/Fs in process emissions. Weak smouldering had low levels of PCDD/Fs (emissions factor: 3.3 ± 0.3 µg TEQ/Mg dried sludge destroyed), levels less than uncontrolled emissions from commercial incinerators. Overall, smouldering acted as a sink for PCDD/Fs, as only 0-3% of the PCDD/Fs originally present in the sludge were released in the emissions, and >99% of the remainder were destroyed with <1% remaining in post-treatment ash. No evidence was found to support de novo synthesis or precursor reactions forming new PCDD/Fs. In addition, 94-100% of all the PTEs analyzed were retained in the post-smouldered material. These results indicate that only minimal emissions treatment for PTEs, PCDD/Fs, and VOCs may be necessary for future sewage sludge smouldering systems. These low emissions risks combined with its unique ability to handle high moisture content waste, indicate that smouldering has significant potential as a valuable waste management technique.

[Full-cycle Health Management of Multiple Myeloma].

Multiple myeloma is a hematologic tumor characterized by clonal proliferation of plasma cells.The development of novel agents and immunotherapy have substantially improved the prognosis of multiple myeloma,with an expectable median survival beyond ten years.Therefore,there is an urgent need to improve the management of this disease.Health management is effective in controlling chronic diseases and full-cycle management should be implemented from the early to the end stage of the disease.Implanting the full-cycle concept into the health management of multiple myeloma will guide and standardize the advances in this field.This review focuses on the full-cycle concept of multiple myeloma and the corresponding application of health management at each stage of the cycle.

Immunoparesis defined by heavy/light chain pair suppression in smoldering multiple myeloma shows initial isotype specificity and involves other isotypes in advanced disease.

Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous plasma cell disorder, with a highly variable clinical course. Immunoparesis, defined by total immunoglobulin measurements, has been shown to be an independent risk factor for progression to symptomatic disease. The heavy/light chain (HLC) assay allows precise measurement of the polyclonal immunoglobulin of the same isotype, enabling the evaluation of isotype-matched immunoparesis (IMI). In this study, we prospectively characterized immunoparesis, as determined by HLC measurements, in 53 SMM patients. Severe IMI was present in 51% of patients, while severe IP of uninvolved isotypes (HLC IP) was present in 39%. Most of the patients with severe HLC IP presented with severe IMI, but not the other way around. Isotype specificity of immune suppression was suggested by lower relative values of isotype-matched HLC pairs, both for IgG and IgA SMM. Severe IMI was associated with other risk factors for progression while patients with severe IMI and severe HLC IP showed an even higher risk profile. Both severe IMI and severe IgM HLC IP showed a significantly shorter time to progression. Finally, gene expression analysis demonstrated differences in the bone marrow microenvironment between patients with IMI and IMI plus HLC IP, with an increased expression of genes associated with cytolytic cells. In conclusion, our data supports isotype specificity of early immunoglobulin suppression mechanisms. While suppression of both involved and uninvolved isotypes is associated with risk of progression, the later appears to develop with more advanced disease and could be mediated by different mechanisms.

Baseline serum B-cell maturation antigen levels predict time to disease progression for patients with smoldering multiple myeloma.

Multiple myeloma (MM) patients with smoldering (S) disease are defined by a lack of CRAB/SLiM criteria but may transform into disease requiring treatment. The International Myeloma Working Group risk stratification model for SMM uses serum M-protein, serum-free light chain ratio, and bone marrow plasma cell percentage. We investigated whether baseline serum B-cell maturation antigen (sBCMA) levels are predictive of disease progression among 65 patients with SMM. A receiver operating characteristic curve was used to establish a definition for high-risk baseline sBCMA. Mantel Byar analysis was used to examine whether high-risk sBCMA was correlated with shorter time to transformation, and a time-dependent cox proportional hazard was used to determine whether it is independent of other risk factors. A z test for proportions was used to compare the percentage of patients that progressed among high-risk versus low-risk sBCMA patients. A baseline sBCMA level ≥137.5 mg/ml was found to be the optimal cutoff between high- and low-risk SMM patients. Patients with high-risk sBCMA levels had a shorter time to transformation (P = .000332). sBCMA was also higher at the time of transformation than baseline levels (P = .0116). sBCMA was the only variable found to be significantly predictive of time to transformation and additionally was found to be independent of other risk factors. In this study, we have shown for the first time that sBCMA levels predict transformation of SMM to active disease and that these levels increase at the time of transformation. These results are consistent with other studies showing that active MM patients undergoing therapy with higher baseline sBCMA levels are more likely to progress early and its levels increase at the time of disease progression.

Understanding biology to tackle the disease: Multiple myeloma from bench to bedside, and back.

Multiple myeloma (MM) is a cancer of antibody-producing plasma cells. The pathognomonic laboratory finding is a monoclonal immunoglobulin or free light chain in the serum and/or urine in association with bone marrow infiltration by malignant plasma cells. MM develops from a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage termed smoldering multiple myeloma (SMM), which differs from active myeloma by the absence of disease-related end-organ damage. Unlike MGUS and SMM, active MM requires therapy. Over the past 6 decades, major advancements in the care of MM patients have occurred, in particular, the introduction of novel agents (ie, proteasome inhibitors, immunomodulatory agents) and the implementation of hematopoietic stem cell transplantation in suitable candidates. The effectiveness and good tolerability of novel agents allowed for their combined use in induction, consolidation, and maintenance therapy, resulting in deeper and more sustained clinical response and extended progression-free and overall survival. Previously a rapidly lethal cancer with few therapeutic options, MM is the hematologic cancer with the most novel US Food and Drug Administration-approved drugs in the past 15 years. These advances have resulted in more frequent long-term remissions, transforming MM into a chronic illness for many patients.

Assessment of atherosclerosis in multiple myeloma and smoldering myeloma patients using 18F- sodium fluoride PET/CT.

BACKGROUND: To compare the NaF uptake in the thoracic aorta and whole heart, as an early indicator of atherosclerosis, in multiple myeloma (MM) and smoldering multiple myeloma (SMM) patients with a healthy control (HC) group. METHODS: Forty-four untreated myeloma patients (35 MM and nine SMM) and twenty-six age and gender-matched HC subjects were collected. Each individual's NaF uptake in three parts of the aorta (AA: ascending aorta, AR: aortic arch, DA: descending aorta) and the whole heart was segmented. Average global standardized uptake value means were derived by sum of the product of each slice area divided by the sum of those slice areas. Results were reported as target to background ratio (TBR). RESULTS: There was a significant difference between the NaF uptake in the thoracic aorta of myeloma and HC groups [AA (myeloma = 1.82 ± 0.21, HC = 1.24 ± 0.02), AR (myeloma = 1.71 ± 0.19, HC = 1.28 ± 0.03) and DA (myeloma = 1.96 ± 0.28, HC = 1.38 ± 0.03); P-values < 0.001]. The difference in the whole heart NaF uptake between two groups was also significant (P < 0.001). CONCLUSIONS: We observed a higher uptake of NaF in the thoracic aorta and whole heart of myeloma patients in comparison to the matched control group.