Practical management of disease-related manifestations and drug toxicities in patients with multiple myeloma.

Multiple myeloma (MM) is a very heterogeneous disease with multiple symptoms and clinical manifestations. MM affects mainly elderly patients and is difficult to manage in the presence of comorbidities, polypharmacy, frailty and adverse events of disease-targeted drugs. The rapid changes in MM treatment resulting from constant innovations in this area, together with the introduction of numerous new drugs with distinct mechanisms of action and toxicity profiles, have led to an increased complexity in the therapeutic decision-making and patient management processes. The prolonged exposure to novel agents, sometimes in combination with conventional therapies, makes this management even more challenging. A careful balance between treatment efficacy and its tolerability should be considered for every patient. During treatment, a close monitoring of comorbidities, disease-related manifestations and treatment side effects is recommended, as well as a proactive approach, with reinforcement of information and patient awareness for the early recognition of adverse events, allowing prompt therapeutic adjustments. In this review, we discuss various issues that must be considered in the treatment of MM patients, while giving practical guidance for monitoring, prevention and management of myeloma-related manifestations and treatment-related toxicities.

Healthcare Resource Utilization and Cost-of-Illness in Systemic Light Chain (AL) Amyloidosis in Europe: Results From the Real-World, Retrospective EMN23 Study.

OBJECTIVES: To report healthcare resource utilization (HCRU) and safety outcomes in systemic light chain (AL) amyloidosis from the EMN23 study. MATERIALS AND METHODS: The retrospective, observational, multinational EMN23 study included 4,480 patients initiating first-line treatment for AL amyloidosis in 2004-2018 and assessed, among other objectives, HCRU and safety outcomes. HCRU included hospitalizations, examinations, and dialysis; safety included serious adverse events (SAEs) and adverse events of special interest (AESIs). Data were descriptively analyzed by select prognostic factors (e.g., cardiac staging by Mayo2004/European) for 2004-2010 and 2011-2018. A cost-of-illness analysis was conducted for the UK and Spain. RESULTS: HCRU/safety and dialysis data were extracted for 674 and 774 patients, respectively. Of patients with assessed cardiac stage (2004-2010: 159; 2011-2018: 387), 67.9% and 61.0% had ≥ 1 hospitalization, 56.0% and 51.4% had ≥ 1 SAE, and 31.4% and 28.9% had ≥ 1 AESI across all cardiac stages in 2004-2010 and 2011-2018, respectively. The per-patient-per-year length of hospitalization increased with disease severity (cardiac stage). Of patients with dialysis data (2004-2010: 176; 2011-2018: 453), 23.9% and 14.8% had ≥ 1 dialysis session across all cardiac stages in 2004-2010 and 2011-2018, respectively. The annual cost-of-illness was estimated at €40,961,066 and €31,904,386 for the UK and Spain, respectively; dialysis accounted for ∼28% (UK) and ∼35% (Spain) of the total AL amyloidosis costs. CONCLUSIONS: EMN23 showed that the burden of AL amyloidosis is substantial, highlighting the need for early disease diagnosis and effective treatments targeting the underlying pathology.

Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) positivity after first-line treatment with autologous stem cell transplantation (ASCT) in multiple myeloma is strongly correlated with reduced progression-free and overall survival. However, PET-positive patients who achieve PET negativity after treatment seem to have comparable outcomes to patients who were PET negative at diagnosis. Hence, giving PET-positive patients additional treatment may improve their outcome. In this phase II study, we screened first-line patients with very good partial response (VGPR) or better after ASCT with PET. PET-positive patients received four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Flow cytometry-based minimal residual disease (MRD) analysis was performed before and after treatment for correlation with PET. Overall, 159 patients were screened with PET. A total of 53 patients (33%) were PET positive and 57% of PET-positive patients were MRD negative, demonstrating that these response assessments are complementary. KRd consolidation converted 33% of PET-positive patients into PET negativity. MRD-negative patients were more likely to convert than MRD-positive patients. In summary, PET after ASCT detected residual disease in a substantial proportion of patients in VGPR or better, even in patients who were MRD negative, and KRd consolidation treatment changed PET status in 33% of patients.

[Multiple Myeloma Treatment Guidelines by the Portuguese Group of Multiple Myeloma]. / Recomendações do Grupo Português do Mieloma Múltiplo para Tratamento do Mieloma Múltiplo.

The treatment of multiple myeloma has profoundly changed with the introduction of several innovative therapies. The optimization of therapeutic sequencing through the combined use of the various drugs developed in recent years and the attention given to the characteristics of patients have allowed the reduction of toxicities and increased survival and quality of life of patients with multiple myeloma. These treatment recommendations from the Portuguese Multiple Myeloma Group offer guidance for first-line treatment and progression/relapse situations. These recommendations are given highlighting the data that justify each choice and referring to the respective levels of evidence that support these options. Whenever possible, the respective national regulatory framework is presented. These recommendations constitute an advance towards the best treatment of multiple myeloma in Portugal.

O tratamento do mieloma múltiplo tem sido amplamente alterado com introdução de várias terapêuticas inovadoras. A otimização da sequenciação terapêutica através do uso combinado dos vários fármacos desenvolvidos nos últimos anos e a atenção dada às características dos doentes têm permitido diminuir toxicidades e aumentar a sobrevivência dos doentes, bem como aumentar a sua qualidade de vida. As presentes recomendações terapêuticas do Grupo Português do Mieloma Múltiplo oferecem orientações para o tratamento de primeira linha e progressão/recaída. As recomendações são fundamentadas evidenciando os dados que justificam cada escolha e referindo os respetivos níveis de evidência que suportam essas opções. Sempre que possível é apresentado o respetivo enquadramento regulamentar nacional. Estas recomendações constituem um avanço para o melhor tratamento do mieloma múltiplo em Portugal.

Evaluation of Semiautomatic and Deep Learning-Based Fully Automatic Segmentation Methods on [18F]FDG PET/CT Images from Patients with Lymphoma: Influence on Tumor Characterization.

The objective is to assess the performance of seven semiautomatic and two fully automatic segmentation methods on [18F]FDG PET/CT lymphoma images and evaluate their influence on tumor quantification. All lymphoma lesions identified in 65 whole-body [18F]FDG PET/CT staging images were segmented by two experienced observers using manual and semiautomatic methods. Semiautomatic segmentation using absolute and relative thresholds, k-means and Bayesian clustering, and a self-adaptive configuration (SAC) of k-means and Bayesian was applied. Three state-of-the-art deep learning-based segmentations methods using a 3D U-Net architecture were also applied. One was semiautomatic and two were fully automatic, of which one is publicly available. Dice coefficient (DC) measured segmentation overlap, considering manual segmentation the ground truth. Lymphoma lesions were characterized by 31 features. Intraclass correlation coefficient (ICC) assessed features agreement between different segmentation methods. Nine hundred twenty [18F]FDG-avid lesions were identified. The SAC Bayesian method achieved the highest median intra-observer DC (0.87). Inter-observers' DC was higher for SAC Bayesian than manual segmentation (0.94 vs 0.84, p < 0.001). Semiautomatic deep learning-based median DC was promising (0.83 (Obs1), 0.79 (Obs2)). Threshold-based methods and publicly available 3D U-Net gave poorer results (0.56 ≤ DC ≤ 0.68). Maximum, mean, and peak standardized uptake values, metabolic tumor volume, and total lesion glycolysis showed excellent agreement (ICC ≥ 0.92) between manual and SAC Bayesian segmentation methods. The SAC Bayesian classifier is more reproducible and produces similar lesion features compared to manual segmentation, giving the best concordant results of all other methods. Deep learning-based segmentation can achieve overall good segmentation results but failed in few patients impacting patients' clinical evaluation.

The management of light chain (AL) amyloidosis in Europe: clinical characteristics, treatment patterns, and efficacy outcomes between 2004 and 2018.

Systemic light-chain (AL) amyloidosis is a rare and debilitating disease. Advances have been made in new treatments in recent years, yet real-world data on the management of the disease are scarce. EMN23 is a retrospective, observational study of patients who initiated first-line treatment in 2004-2018 in Europe, presenting the demographics, clinical characteristics, treatment patterns, and outcomes, from 4480 patients. Regimens based on bortezomib were the most frequently used as first-line therapy; only 6.2% of the patients received autologous stem cell transplant. Hematologic responses improved post-2010 (67.1% vs 55.6% pre-2010). The median overall survival (OS) was 48.8 (45.2-51.7) months; 51.4 (47.3-57.7) months pre-2010 and 46.7 (41.3-52.2) months post-2010. Early mortality was 13.4% and did not improve (11.4% vs 14.4% pre- and post-2010); furthermore, it remained high in patients with advanced cardiac disease (over 39% for stage IIIb). There was a significant improvement for stage IIIa (14.2 vs 30.7 months, p = 0.0170) but no improvement for stage IIIb patients (5.0 vs 4.5 months). This European real-world study of AL-amyloidosis emphasizes the unmet needs of early diagnosis, and the lack of improvement in survival outcomes of the frail stage IIIb population, despite the introduction of new therapies in recent years.

Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.

Bruton's tyrosine kinase (BTK) is a member of the TEC-family kinases and crucial for the proliferation and differentiation of B-cells. We evaluated the therapeutic potential of a covalent inhibitor (JS25) with nanomolar potency against BTK and with a more desirable selectivity and inhibitory profile compared to the FDA-approved BTK inhibitors ibrutinib and acalabrutinib. Structural prediction of the BTK/JS25 complex revealed sequestration of Tyr551 that leads to BTK's inactivation. JS25 also inhibited the proliferation of myeloid and lymphoid B-cell cancer cell lines. Its therapeutic potential was further tested against ibrutinib in preclinical models of B-cell cancers. JS25 treatment induced a more pronounced cell death in a murine xenograft model of Burkitt's lymphoma, causing a 30-40% reduction of the subcutaneous tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. In a patient model of diffuse large B-cell lymphoma, the drug response of JS25 was higher than that of ibrutinib, leading to a 64% "on-target" efficacy. Finally, in zebrafish patient-derived xenografts of chronic lymphocytic leukemia, JS25 was faster and more effective in decreasing tumor burden, producing superior therapeutic effects compared to ibrutinib. We expect JS25 to become therapeutically relevant as a BTK inhibitor and to find applications in the treatment of hematological cancers and other pathologies with unmet clinical treatment.

Successful treatment of persistent and severe SARS-CoV-2 infection in a high-risk chronic lymphocytic leukemia patient using Ronapreve™ antibodies.

Patients with lymphoproliferative diseases are at an increased risk of an incomplete immune response following vaccination or SARS-CoV-2 infection and might develop persistent viral infection and severe COVID-19 disease. We present a case of successful treatment of persistent and mechanical-ventilation-requiring SARS-CoV-2 infection in a del17+ CLL patient using exogenous antibodies.

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine-Are We There Yet?

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients' bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.

Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment.

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

Patient-Derived Extracellular Vesicles Proteins as New Biomarkers in Multiple Myeloma - A Real-World Study.

Multiple myeloma (MM) is a hematological malignancy of clonal antibody-secreting plasma cells (PCs). MM diagnosis and risk stratification rely on bone marrow (BM) biopsy, an invasive procedure prone to sample bias. Liquid biopsies, such as extracellular vesicles (EV) in peripheral blood (PB), hold promise as new minimally invasive tools. Real-world studies analyzing patient-derived EV proteome are rare. Here, we characterized a small EV protein content from PB and BM samples in a cohort of 102 monoclonal gammopathies patients routinely followed in the clinic and 223 PB and 111 BM samples were included. We investigated whether EV protein and particle concentration could predict an MM patient prognosis. We found that a high EV protein/particle ratio, or EV cargo >0.6 µg/108 particles, is related to poorer survival and immune dysfunction. These results were supported at the protein level by mass spectrometry. We report a set of PB EV-proteins (PDIA3, C4BPA, BTN1A1, and TNFSF13) with a new biomarker potential for myeloma patient outcomes. The high proteomic similarity between PB and BM matched pairs supports the use of circulating EV as a counterpart of the BM EV proteome. Overall, we found that the EV protein content is related to patient outcomes, such as survival, immune dysfunction, and possibly treatment response.

Boosting Immunity against Multiple Myeloma.

Despite the improvement of patient's outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody-drug conjugates or bispecific antibodies broadened the possibility of improving patients' survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group.

This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.

The Immune Microenvironment in Multiple Myeloma: Friend or Foe?

Multiple myeloma (MM) is one of the most prevalent hematological cancers worldwide, characterized by the clonal expansion of neoplastic plasma cells in the bone marrow (BM). A combination of factors is implicated in disease progression, including BM immune microenvironment changes. Increasing evidence suggests that the disruption of immunological processes responsible for myeloma control ultimately leads to the escape from immune surveillance and resistance to immune effector function, resulting in an active form of myeloma. In fact, one of the hallmarks of MM is the development of a permissive BM milieu that provides a growth advantage to the malignant cells. Consequently, a better understanding of how myeloma cells interact with the BM niche compartments and disrupt the immune homeostasis is of utmost importance to develop more effective treatments. This review focuses on the most up-to-date knowledge regarding microenvironment-related mechanisms behind MM immune evasion and suppression, as well as promising molecules that are currently under pre-clinical tests targeting immune populations.

Multiple Myeloma in Portugal: Burden of Disease and Cost of Illness.

BACKGROUND: Multiple myeloma (MM) is the second most common hematological cancer worldwide and has significant morbidity and mortality and is increasing in incidence. While MM management costs are considerable, specific economic data at the country level remain scarce. OBJECTIVE: This study assesses the burden and cost of MM in Portugal from the perspective of the National Health Service (NHS) to support the definition of health policies, resource allocation and patient care. METHODS: Developed by the Portuguese Multiple Myeloma Group, this study considers the most recent available data. Burden of disease was measured using disability-adjusted life-years (DALYs). The cost of MM was estimated using a prevalence-based model that estimated direct costs for the NHS considering all costs associated with diagnosis, hospitalizations, surgeries, emergency visits, medical appointments, drugs and transportation. Costs were quantified based on the diagnosis-related group funding price, except for drug usage, which was calculated using the average hospital product stock price. RESULTS: The burden of disease attributable to MM for 2018 was estimated at 8931 DALYs: 8570 resulting from premature deaths and 361 from disability. Average yearly direct costs per patients with MM amounted to €31,449 (year 2018 values). Total direct costs are estimated at €61 million per year. CONCLUSIONS: The mortality rate in MM means that most DALYs are due to years of life lost rather than years lost due to disability. This study generates comprehensive data on the burden and cost of MM in Portugal and provides updated insights into the costs associated with the management of MM.

Management of older and frail patients with multiple myeloma in the Portuguese routine clinical practice: Deliberations and recommendations from an expert panel of hematologists.

The management of older patients with Multiple Myeloma (MM) is particularly challenging due to the highly heterogeneous nature of this population, both in terms of physical and cognitive functioning. Older patients may be divided into fit, intermediate and frail, with variable abilities to tolerate treatments. A careful and correct assessment of the frailty status is thus paramount for the success of therapy and for improving outcomes. With the aging of the European population, the number of older patients with MM is rapidly growing. We hereby present the deliberations and recommendations from an expert panel of Portuguese hematologists conducted to discuss the management of this population, including how to stratify and treat older patients with MM according to their frailty status. The use of frailty tools is critical for the development of individualized risk-adapted treatment strategies and to minimize the risk of under or overtreatment. Aggressive therapies should be used in fitter patients to improve survival outcomes, while frail patients should generally be treated with less toxic approaches to control symptoms while minimizing toxicity. In intermediate-fit patients, low-dose triplets are recommended to achieve a balance between improving survival and maintaining quality of life. The management of older patients with MM should be performed by a multidisciplinary team in view of their advanced age and high prevalence of comorbidities. The inclusion of older and frail patients in future clinical trials investigating treatment regimens for MM is crucial to evaluate treatment feasibility and to improve clinical decision making in this population.

Liquid biopsies for multiple myeloma in a time of precision medicine.

Multiple myeloma (MM) is a challenging, progressive, and highly heterogeneous hematological malignancy. MM is characterized by multifocal proliferation of neoplastic plasma cells in the bone marrow (BM) and sometimes in extramedullary organs. Despite the availability of novel drugs and the longer median overall survival, some patients survive more than 10 years while others die rapidly. This heterogeneity is mainly driven by biological characteristics of MM cells, including genetic abnormalities. Disease progressions are mainly due to the inability of drugs to overcome refractory disease and inevitable drug-resistant relapse. In clinical practice, a bone marrow biopsy, mostly performed in one site, is still used to access the genetics of MM. However, BM biopsy use is limited by its invasive nature and by often not accurately reflecting the mutational profile of MM. Recent insights into the genetic landscape of MM provide a valuable opportunity to implement precision medicine approaches aiming to enable better patient profiling and selection of targeted therapies. In this review, we explore the use of the emerging field of liquid biopsies in myeloma patients considering current unmet medical needs, such as assessing the dynamic mutational landscape of myeloma, early predictors of treatment response, and a less invasive response monitoring.

Quantification of tumor burden in multiple myeloma by atlas-based semi-automatic segmentation of WB-DWI.

BACKGROUND: Whole-body diffusion weighted imaging (WB-DWI) has proven value to detect multiple myeloma (MM) lesions. However, the large volume of imaging data and the presence of numerous lesions makes the reading process challenging. The aim of the current study was to develop a semi-automatic lesion segmentation algorithm for WB-DWI images in MM patients and to evaluate this smart-algorithm (SA) performance by comparing it to the manual segmentations performed by radiologists. METHODS: An atlas-based segmentation was developed to remove the high-signal intensity normal tissues on WB-DWI and to restrict the lesion area to the skeleton. Then, an outlier threshold-based segmentation was applied to WB-DWI images, and the segmented area's signal intensity was compared to the average signal intensity of a low-fat muscle on T1-weighted images. This method was validated in 22 whole-body DWI images of patients diagnosed with MM. Dice similarity coefficient (DSC), sensitivity and positive predictive value (PPV) were computed to evaluate the SA performance against the gold standard (GS) and to compare with the radiologists. A non-parametric Wilcoxon test was also performed. Apparent diffusion coefficient (ADC) histogram metrics and lesion volume were extracted for the GS segmentation and for the correctly identified lesions by SA and their correlation was assessed. RESULTS: The mean inter-radiologists DSC was 0.323 ± 0.268. The SA vs GS achieved a DSC of 0.274 ± 0.227, sensitivity of 0.764 ± 0.276 and PPV 0.217 ± 0.207. Its distribution was not significantly different from the mean DSC of inter-radiologist segmentation (p = 0.108, Wilcoxon test). ADC and lesion volume intraclass correlation coefficient (ICC) of the GS and of the correctly identified lesions by the SA was 0.996 for the median and 0.894 for the lesion volume (p < 0.001). The duration of the lesion volume segmentation by the SA was, on average, 10.22 ± 0.86 min, per patient. CONCLUSIONS: The SA provides equally reproducible segmentation results when compared to the manual segmentation of radiologists. Thus, the proposed method offers robust and efficient segmentation of MM lesions on WB-DWI. This method may aid accurate assessment of tumor burden and therefore provide insights to treatment response assessment.

Definition of Immunological Nonresponse to Antiretroviral Therapy: A Systematic Review.

BACKGROUND: Terms and criteria to classify people living with HIV on antiretroviral therapy who fail to achieve satisfactory CD4 T-cell counts are heterogeneous, and need revision and summarization. METHODS: We performed a systematic review of PubMed original research articles containing a set of predefined terms, published in English between January 2009 and September 2018. The search retrieved initially 1360 studies, of which 103 were eligible. The representative terminology and criteria were extracted and analyzed. RESULTS: Twenty-two terms and 73 criteria to define the condition were identified. The most frequent term was "immunological nonresponders" and the most frequent criterion was "CD4 T-cell count <350 cells/µL after ≥24 months of virologic suppression." Most criteria use CD4+ T-cell counts as a surrogate, either as an absolute value or as a change after a defined period of time [corrected]. Distinct values and time points were used. Only 9 of the 73 criteria were used by more than one independent research team. Herein we propose 2 criteria that could help to reach a consensus. CONCLUSIONS: The high disparity in terms and criteria here reported precludes data aggregation and progression of the knowledge on this condition, because it renders impossible to compare data from different studies. This review will foster the discussion of terms and criteria to achieve a consensual definition.

International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders.

Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in the investigation of multiple myeloma and often dictates the decision to start treatment. Furthermore, detection of minimal residual disease is important for prognosis determination and treatment planning, and it has underscored an unmet need for sensitive imaging methods that accurately assess patient response to multiple myeloma treatment. Low-dose whole-body CT has increased sensitivity compared with conventional skeletal survey in the detection of bone disease, which can reveal information leading to changes in therapy and disease management that could prevent or delay the onset of clinically significant morbidity and mortality as a result of skeletal-related events. Given the multiple options available for the detection of bone and bone marrow lesions, ranging from conventional skeletal survey to whole-body CT, PET/CT, and MRI, the International Myeloma Working Group decided to establish guidelines on optimal use of imaging methods at different disease stages. These recommendations on imaging within and outside of clinical trials will help standardise imaging for monoclonal plasma cell disorders worldwide to allow the comparison of results and the unification of treatment approaches for multiple myeloma.