The two main diffuse patterns are 12: numerous, well-circumscribed, lytic bone lesions (70% of cases 14), often associated with vertebral compression fractures/vertebra plana. Anemia: A reduced number of red blood cells that can cause weakness, a reduced ability to exercise, shortness of breath, and dizziness. Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Lancet Haematol. FDG PET-CT is effective in identifying the distribution of disease 14. The concordance between NGF and NGS is high. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. An analysis of the PETHEMA/GEM2012MENOS65 trial showed that MRD-negative responses were able to overcome poor prognostic features at diagnosis, including Revised International Staging System stage III.34,35  Similar observations were seen for patients with high-risk cytogenetics in IFM 2009 and earlier PETHEMA/GEM trials.31,36  The findings with MRD extend on previous observations where achieving CR was especially important in high-risk disease defined by gene expression profiling.37. ~40% bone destruction is required for lesion detection, thus giving the skeletal survey a high false-negative rate of ~50% (range 30-70%) 12. Patients who are MRD negative by NGS (10−5) after auto-SCT discontinue treatment, whereas patients who are MRD positive continue to undergo consolidation with dara-KRd for up to 2 cycles until MRD negative. doi: https://doi.org/10.1182/hematology.2021000230. This was initially shown with flow cytometry with sensitivity down to 10−4 and where each log reduction in MRD translated into improvement in median OS.29  In the Francophone du Myélome 2009 study of upfront vs deferred auto-SCT after initial therapy with lenalidomide, bortezomib, and dexamethasone, MRD status was assessed by flow cytometry in all patients, and a subset of these patients was evaluated by more sensitive NGS.30,31  Patients who were able to achieve MRD negative status at 10−6 by NGS, which is deeper than the recommended IMWG threshold of 10−5, had superior outcomes in PFS and OS compared with MRD-positive status (Figure 1).31  Moreover, the study showed differences in outcomes between 10−6, 10−5, and 10−4. Primer of Diagnostic Imaging. 2022 Feb 1;327(5):497. doi: 10.1001/jama.2021.25306. The term minimal residual disease conventionally refers to disease in the bone marrow space. Radiology Review Manual. Meaney et al. Common Causes The exact causes of multiple myeloma have not been established. The various immunoglobulins have different functions in the body. Patients and Methods Clinical and laboratory data were gathered on 10,750 previously untreated symptomatic myeloma patients from 17 institutions, including sites in North America, Europe, and Asia. For example, in the IMAgerie du JEune Myélome study of the Intergroupe Francophone du Myélome 2009 trial, 26% of patients with MRD-negative disease by flow cytometry (sensitivity 10−4) had positive positron emission tomography (PET) computed tomography (CT) findings.49  Similar findings were seen in the CASSIOPET substudy of CASSIOPEIA, in which 10.5% of patients who were negative by NGF at 10−5 had positive PET CT.50  This discrepancy is relevant, as patients who were MRD negative but PET CT positive had similar outcomes to patients who were MRD positive. Before Whole-body low dose CT is also better to assess the risk of pathological fracture in severely affected bones as well as the presence of extramedullary lesions 12. Beschwerden treten häufig erst im fortgeschrittenen Stadium auf. Hanrahan C, Christensen C, Crim J. Currently, multiple myeloma remains incurable with a median survival of 5.5 years (range <6 months to >10 years) 14. Although there are maturing data on how it adds new prognostic power, there is a lag in the data for how to effectively use the test to make treatment decisions. 2005;55(1):56-63. Importance: Multiple myeloma is a hematologic malignancy characterized by presence of abnormal clonal plasma cells in the bone marrow, with potential for uncontrolled growth causing destructive bone lesions, kidney injury, anemia, and hypercalcemia. In 1 series, a trackable sequence for NGS could not be identified in 7.8% of samples.20  NGF also has the advantage of assessing for hemodilution by looking for mast cell, erythroblast, and B-cell precursor populations.12  Finally, from a research perspective, NGF may be able to evaluate the bone marrow microenvironment, which may have prognostic relevance. Get the latest news and education delivered to your inbox, Receive an email when new articles are posted on, Please provide your email address to receive an email when new articles are posted on. It arises from red marrow due to the monoclonal proliferation of plasma cells and manifests in a wide range of radiographic abnormalities. Current Concepts in the Evaluation of Multiple Myeloma with MR Imaging and FDG PET/CT. 2023 May 20;7(1):46. doi: 10.1038/s41698-023-00385-w. Nishiwaki S, Sugiura I, Sato T, Kobayashi M, Osaki M, Sawa M, Adachi Y, Okabe M, Saito S, Morishita T, Kohno A, Nishiyama T, Iida H, Kurahashi S, Kuwatsuka Y, Sugiyama D, Ito S, Nishikawa H, Kiyoi H. EJHaem. It has a very specific adverse event profile, which makes it complex because we need to work hand-in-hand with our ophthalmologists. pneumonia due to leukopenia, plasmacytomas typically progress to multiple myeloma. reverse albumin/globulin ratio (i.e. Bone scintigraphy appearances of disseminated multiple myeloma is variable due to the potential lack of osteoblastic activity. Multiple myeloma ( MM ), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Smoldering Multiple Myeloma Requiring Treatment: Time for a New Definition? Lesions are sclerotic in only 3% of patients 7. The .gov means it’s official. At the time the article was last revised Eid Kakish had no recorded disclosures. Delorme S & Baur-Melnyk A. [6] Often, no symptoms are noticed initially. However, a limitation in treating patients for relapse by MRD criteria is that current clinical trials generally require measurable disease, and MRD positivity is not considered measurable to be eligible for the trial. The average patient for whom we use belantamab mafodotin in the U.S. is pomalidomide-refractory and would not have been eligible for this study. Indeed, analysis of peripheral blood provides a systemic assessment and avoids the pitfalls of heterogeneity in bone marrow sampling. An ongoing question is the optimal timing of treating relapsed disease. Additional disease-related complications include . The most popular staging system, the International Staging System, uses the combination of β2-microglobulin test and serum albumin 6. The combo immunotherapy regimen, which is designed to target antigens on myeloma cells, demonstrated an overall response rate (ORR) of 86.6% (71 of 82 patients) across all dose levels. [10] As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. ML-based sequential analysis to assist selection between VMP and RD for newly diagnosed multiple myeloma. A type of white blood cell . 10. “While this study did not meet its primary objective or demonstrating PFS superiority, single-agent [belantamab mafodotin] appears to show similar levels of clinical activity to a doublet regimen in relapsed or refractory multiple myeloma,” Katja Weisel, MD, deputy director and professor of hematology/oncology in the department of oncology, hematology and bone marrow transplantation at University Medical Center Hamburg-Eppendorf in Germany, said during a presentation. Belantamab mafodotin-blmf is an antibody-drug conjugate comprising a humanized B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a noncleavable linker. Das Multiple Myelom ist eine bösartige Erkrankung der Plasmazellen im Knochenmark und gehört zu den Krebserkrankungen des blutbildenden Systems. Use their search tool to find a support group in your area. The Multiple Myeloma Research Foundation (MMRF) is a nonprofit that offers a variety of services for people with multiple myeloma. Progression-free survival improves with each log reduction in MRD in IFM 2009 in patients who achieved at least a very good partial response. Check for errors and try again. A 57-year-old woman with multiple myeloma (MM) has completed initial therapy with lenalidomide, bortezomib, and dexamethasone, followed by high-dose melphalan and autologous stem cell transplant (auto-SCT). Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. This is the American ICD-10-CM version of C90.00 - other international versions of ICD-10 C90.00 may differ. Accessibility She is on maintenance therapy with lenalidomide and ixazomib. Among all patients with multiple myeloma, standard first-line (induction) therapy consists of a combination of an injectable proteasome inhibitor (ie, bortezomib), an oral immunomodulatory agent (ie, lenalidomide), and dexamethasone and is associated with median progression-free survival of 41 months, compared with historical reports of 8.5 months without therapy. Larger lesions may be either hyperactive (hot) or photopenic (cold). MRI is more sensitive in detecting multiple lesions compared to the standard plain film skeletal survey and CT 8,12. Hematology Am Soc Hematol Educ Program. In the PERSEUS trial (NCT03710603), patients on maintenance with daratumumab and lenalidomide who are MRD negative can discontinue daratumumab and continue on lenalidomide. 1 The NCCN Multiple Myeloma Panel . 2020 Jun;7(6):e456-e468. Reference article, Radiopaedia.org (Accessed on 07 Jun 2023) https://doi.org/10.53347/rID-9555, {"containerId":"expandableQuestionsContainer","displayRelatedArticles":true,"displayNextQuestion":true,"displaySkipQuestion":true,"articleId":9555,"questionManager":null,"mcqUrl":"https://radiopaedia.org/articles/multiple-myeloma-1/questions/2230?lang=us"}. F-18 FDG uptake by the myeloma lesions corresponds to lytic bone lesions or soft tissue plasmacytomas seen on CT. Andrew J. Yee: no off-label drug use discussed. Subsequent evaluations can be used to further specify the duration of negativity (eg, MRD negative at 5 years). Epub 2021 Apr 19. Multiple myeloma and osteosarcoma combined account for ~50% of all primary bone malignancies 7. Secondary endpoints included overall response rate, OS, duration of response and safety. CHICAGO — Belantamab mafodotin monotherapy did not significantly extend PFS compared with the combination of pomalidomide and dexamethasone among adults with relapsed or refractory multiple myeloma, phase 3 study results showed. Overall, the field is fortunate that newer treatments are leading to unprecedented depths of response that require newer methods such as NGS or NGF to measure their effect. 2010;30(1):127-42. Unchecked, the excess production of these plasma cells can ultimately lead to specific end-organ damage. Search for other works by this author on: Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma, Safety and effectiveness of weekly carfilzomib, lenalidomide, dexamethasone, and daratumumab combination therapy for patients with newly diagnosed multiple myeloma: the MANHATTAN nonrandomized clinical trial, Complete response correlates with long-term survival and progression-free survival in high-dose therapy in multiple myeloma, Association between complete response and outcomes in transplant-eligible myeloma patients in the era of novel agents, Grupo Español de MM; Programa para el Estudio de la Terapé utica en Hemopatía Maligna, Long-term prognostic significance of response in multiple myeloma after stem cell transplantation, Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients, Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial, Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial, International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma, Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders, GEM (Grupo Español de MM)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Groups, Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation, Next generation flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma, Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma, Analytical evaluation of the clonoSEQ assay for establishing measurable (minimal) residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma, Minimal residual disease evaluation by multiparameter flow cytometry and next generation sequencing in the Forte trial for newly diagnosed multiple myeloma patients, Concordance of post- consolidation minimal residual disease rates by multiparametric flow cytometry and next-generation sequencing in CASSIOPEIA, Comparison of next-generation sequencing (NGS) and next-generation flow (NGF) for minimal residual disease (MRD) assessment in multiple myeloma, Routine evaluation of minimal residual disease in myeloma using next-generation sequencing clonality testing: feasibility, challenges, and direct comparison with high-sensitivity flow cytometry, Moffitt cancer center 2-year single-institution experience with next-generation sequencing minimal residual disease detection: clinical utility, application, and correlation with outcomes in plasma cell and lymphoid malignancies, Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis, Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis, A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma, International harmonization in performing and reporting minimal residual disease assessment in multiple myeloma trials, Minimal residual disease in myeloma: application for clinical care and new drug registration [published online 28 July 2021], Minimal residual disease as a potential surrogate end point-lingering questions, The role of minimal residual disease testing in myeloma treatment selection and drug development: current value and future applications, Summary of the third annual blood and marrow transplant clinical trials network myeloma intergroup workshop on minimal residual disease and immune profiling, Minimal residual disease in myeloma by flow cytometry: independent prediction of survival benefit per log reduction, Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma, Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma, Efficacy of daratumumab (DARA)+ bortezomib/thalidomide/dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM) based on minimal residual disease (MRD) status: analysis of the CASSIOPEIA trial, Impact of minimal residual disease (MRD) by multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) on outcome: results of newly diagnosed transplant-eligible multiple myeloma (MM) patients enrolled in the forte trial, GEM (Grupo Español de Mieloma)/PETHEMA (Programa Para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group, Measurable residual disease by next- generation flow cytometry in multiple myeloma, Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma, GEM (Grupo Español de Mieloma)/PETHEMA (Programa para el Estudio de la Terapéutica en Hemopatías Malignas) Cooperative Study Group, Depth of response in multiple myeloma: a pooled analysis of three PETHEMA/GEM clinical trials, Benefit of complete response in multiple myeloma limited to high-risk subgroup identified by gene expression profiling, Complete remission sustained 3 years from treatment initiation is a powerful surrogate for extended survival in multiple myeloma, Relapse after complete response in newly diagnosed multiple myeloma: implications of duration of response and patterns of relapse, Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in total therapy protocols, Evaluation of sustained minimal residual disease negativity with daratumumab-combination regimens in relapsed and/or refractory multiple myeloma: analysis of POLLUX and CASTOR, Sustained minimal residual disease negativity with daratumumab in newly diagnosed multiple myeloma: MAIA and ALCYONE [published online 16 July 2021], Dynamics of minimal residual disease in patients with multiple myeloma on continuous lenalidomide maintenance: a single-arm, single-centre, phase 2 trial, Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival, Minimal residual disease after transplantation or lenalidomide-based consolidation in myeloma patients: a prospective analysis, Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma, Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans, The clinical impact of macrofocal disease in multiple myeloma differs between presentation and relapse, Prospective evaluation of magnetic resonance imaging and [(18)F]fluorodeoxyglucose positron emission tomography-computed tomography at diagnosis and before maintenance therapy in symptomatic patients with multiple myeloma included in the IFM/DFCI 2009 trial: results of the IMAJEM study, Evaluation of the prognostic value of positron emission tomography-computed tomography (PET-CT) at diagnosis and follow-up in transplant-eligible newly diagnosed multiple myeloma (TE NDMM) patients treated in the phase 3 Cassiopeia Study: results of the Cassiopet Companion Study, Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma, Standardization of 18F-FDG-PET/CT according to Deauville criteria for metabolic complete response definition in newly diagnosed multiple myeloma, Complete response in myeloma extends survival without, but not with history of prior monoclonal gammopathy of undetermined significance or smouldering disease, Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis, Clinical value of molecular subtyping multiple myeloma using gene expression profiling, The prognostic value of the depth of response in multiple myeloma depends on the time of assessment, risk status and molecular subtype, Blood monitoring of circulating tumor plasma cells by next generation flow in multiple myeloma after therapy, Myeloma MRD by deep sequencing from circulating tumor DNA does not correlate with results obtained in the bone marrow, Monitoring tumour burden and therapeutic response through analysis of circulating tumour DNA and extracellular RNA in multiple myeloma patients, Genomic discovery and clonal tracking in multiple myeloma by cell-free DNA sequencing, Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report, Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry, Using mass spectrometry to monitor monoclonal immunoglobulins in patients with a monoclonal gammopathy, A universal solution for eliminating false positives in myeloma due to therapeutic monoclonal antibody interference, MASS-FIX versus standard methods to predict for PFS and OS among multiple myeloma patients participating on the STAMINA trial, Analysis of minimal residual disease in bone marrow by NGF and in peripheral blood by mass spectrometry in newly diagnosed multiple myeloma patients enrolled in the GEM2012MENOS65 clinical trial, Measurable residual disease assessed by mass spectrometry in peripheral blood in multiple myeloma in a phase II trial of carfilzomib, lenalidomide, dexamethasone and autologous 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