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2.
Lancet Oncol ; 24(7): e293-e311, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37414019

RESUMO

Here, the International Myeloma Working Group (IMWG) updates its clinical practice recommendations for the management of multiple myeloma-related renal impairment on the basis of data published until Dec 31, 2022. All patients with multiple myeloma and renal impairment should have serum creatinine, estimated glomerular filtration rate, and free light chains (FLCs) measurements together with 24-h urine total protein, electrophoresis, and immunofixation. If non-selective proteinuria (mainly albuminuria) or involved serum FLCs value less than 500 mg/L is detected, then a renal biopsy is needed. The IMWG criteria for the definition of renal response should be used. Supportive care and high-dose dexamethasone are required for all patients with myeloma-induced renal impairment. Mechanical approaches do not increase overall survival. Bortezomib-based regimens are the cornerstone of the management of patients with multiple myeloma and renal impairment at diagnosis. New quadruplet and triplet combinations, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, improve renal and survival outcomes in both newly diagnosed patients and those with relapsed or refractory disease. Conjugated antibodies, chimeric antigen receptor T-cells, and T-cell engagers are well tolerated and effective in patients with moderate renal impairment.


Assuntos
Antineoplásicos , Mieloma Múltiplo , Insuficiência Renal , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Dexametasona , Antineoplásicos/efeitos adversos , Insuficiência Renal/etiologia , Insuficiência Renal/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/uso terapêutico
3.
Br J Haematol ; 203(4): 536-545, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37217164

RESUMO

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.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Estudos Prospectivos , Estudos Retrospectivos , Imagem Corporal Total/métodos , Fluordesoxiglucose F18/uso terapêutico , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos
4.
J Natl Compr Canc Netw ; 21(1): 67-81, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36652935

RESUMO

Primary systemic light chain amyloidosis (SLCA) is characterized by production of light chains that get converted to amyloid fibrils with an affinity for visceral organs and causing organ dysfunction. The therapy for SLCA is directed to recovering the function of the affected organs by targeting the abnormal plasma cell clone and slowing deposition of amyloid fibrils. The NCCN Guidelines for SLCA provide recommendations for workup, diagnosis, and treatment of primary as well as previously treated SLCA.


Assuntos
Amiloide , Amiloidose , Humanos , Amiloidose/diagnóstico , Amiloidose/terapia , Amiloidose/etiologia , Plasmócitos
5.
J Natl Compr Canc Netw ; 21(12): 1281-1301, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38081133

RESUMO

The treatment of relapsed/refractory multiple myeloma (MM) has evolved to include several new options. These include new combinations with second generation proteasome inhibitors (PI); second generation immunomodulators, monoclonal antibodies, CAR T cells, bispecific antibodies, selinexor, venetoclax, and many others. Most patients with MM undergo several cycles of remissions and relapse, and therefore need multiple lines of combination therapies. Selecting treatment options for relapsed/refractory MM requires consideration of resistance status to specific classes, and patient-specific factors such as age and other comorbidities should be considered. The NCCN Guidelines for MM provide a framework on which to base decisions regarding workup, treatment, and follow-up of newly diagnosed and previously treated MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to relapsed/refractory disease.


Assuntos
Mieloma Múltiplo , Humanos , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oncologia , Mieloma Múltiplo/terapia , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico
6.
Skeletal Radiol ; 52(3): 565-583, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35881152

RESUMO

OBJECTIVE: To evaluate the role of diffusion-weighted imaging (DWI) in the initial diagnosis, staging, and assessment of treatment response in patients with multiple myeloma (MM). MATERIALS AND METHODS: A systematic literature review was conducted in PubMed, the Cochrane Library, EMBASE, Scopus, and Web of Science databases. The primary endpoints were defined as the diagnostic performance of DWI for disease detection, staging of MM, and assessing response to treatment in these patients. RESULTS: Of 5881 initially reviewed publications, 33 were included in the final qualitative and quantitative meta-analysis. The diagnostic performance of DWI in the detection of patients with MM revealed pooled sensitivity and specificity of 86% (95% CI: 84-89) and 63% (95% CI: 56-70), respectively, with a diagnostic odds ratio (OR) of 14.98 (95% CI: 4.24-52.91). The pooled risk difference of 0.19 (95% CI: - 0.04-0.42) was reported in favor of upstaging with DWI compared to conventional MRI (P value = 0.1). Treatment response evaluation and ADCmean value changes across different studies showed sensitivity and specificity of approximately 78% (95% CI: 72-83) and 73% (95% CI: 61-83), respectively, with a diagnostic OR of 7.21 in distinguishing responders from non-responders. CONCLUSIONS: DWI is not only a promising tool for the diagnosis of MM, but it is also useful in the initial staging and re-staging of the disease and treatment response assessment. This can aid clinicians with earlier initiation or change in treatment strategy, which could have prognostic significance for patients.


Assuntos
Imagem de Difusão por Ressonância Magnética , Mieloma Múltiplo , Humanos , Imageamento por Ressonância Magnética , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Sensibilidade e Especificidade , Resultado do Tratamento , Estadiamento de Neoplasias
7.
Br J Haematol ; 199(1): 65-75, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35608264

RESUMO

The definition of multiple myeloma (MM) was updated in 2014, with the intent to enable earlier treatment and thereby avoid appearance of end-organ damage at progression from smouldering multiple myeloma (SMM) to MM. The purpose of this study was to investigate to which extent the development of end-organ damage at progression to MM was reduced under the updated guidelines. In this prospective observational cohort study (ClinicalTrials.gov Identifier: NCT01374412), between 2014 and 2020, 96 SMM patients prospectively underwent whole-body magnetic resonance imaging (wb-MRI) and serological follow-up at baseline and every 6 months thereafter. A total of 22 patients progressed into MM during follow-up, of which seven (32%) showed SLiM-criteria only but no end-organ damage. Four (57%) of the seven patients who progressed by SLiM-criteria only progressed with >1 focal lesion (FL) or a growing FL, and three (43%) due to serum free light-chain-ratio ≥100. Fifteen (68%) out of 22 patients who progressed still suffered from end-organ damage at progression. The updated disease definition reduced the proportion of SMM patients suffering from end-organ damage at progression to MM by one third. wb-MRI is an important tool for detection of SMM patients who progress to MM without end-organ damage.


Assuntos
Mieloma Múltiplo , Mieloma Múltiplo Latente , Progressão da Doença , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Mieloma Múltiplo/patologia , Estudos Prospectivos , Mieloma Múltiplo Latente/diagnóstico por imagem , Imagem Corporal Total
8.
J Natl Compr Canc Netw ; 20(1): 91-95, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991076

RESUMO

Venous thromboembolism (VTE) is a major complication in all patients with cancer. Compared with the general population, patients with multiple myeloma (MM) have a 9-fold increase in VTE risk, likely because of their malignancy, its treatments, and other additional patient-related factors. In MM, thromboembolism events tend to occur within 6 months of treatment initiation, regardless of treatment regimen; however, the use of immunomodulatory agents such as thalidomide or lenalidomide, especially in combination with dexamethasone or multiagent chemotherapy, is known to create a significant risk for VTE. Currently, official recommendations for VTE prophylaxis in MM outlined in various national guidelines or multidisciplinary society panels are based on expert opinion, because data from randomized controlled trials are scarce. Large studies which have mainly focused on the efficacy of thromboprophylaxis in patients with cancer at higher risk for VTE either had a very low representation of patients with MM, or excluded them all together, limiting our ability to draw evidence-based conclusions on how to effectively protect MM population from VTE. In this brief perspective, we highlight some of the greatest challenges that have hampered the field concerning the availability of high-quality clinical trial data for the formulation of best VTE prophylaxis strategies in patients with newly diagnosed MM, as well as the rationale for the latest updates in the NCCN Guidelines on this topic.


Assuntos
Mieloma Múltiplo , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Humanos , Lenalidomida/efeitos adversos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Fatores de Risco , Talidomida/efeitos adversos , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
9.
J Natl Compr Canc Netw ; 20(1): 8-19, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991075

RESUMO

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia
10.
Skeletal Radiol ; 51(1): 59-80, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34363522

RESUMO

Bone imaging has been intimately associated with the diagnosis and staging of multiple myeloma (MM) for more than 5 decades, as the presence of bone lesions indicates advanced disease and dictates treatment initiation. The methods used have been evolving, and the historical radiographic skeletal survey has been replaced by whole body CT, whole body MRI (WB-MRI) and [18F]FDG-PET/CT for the detection of bone marrow lesions and less frequent extramedullary plasmacytomas.Beyond diagnosis, imaging methods are expected to provide the clinician with evaluation of the response to treatment. Imaging techniques are consistently challenged as treatments become more and more efficient, inducing profound response, with more subtle residual disease. WB-MRI and FDG-PET/CT are the methods of choice to address these challenges, being able to assess disease progression or response and to detect "minimal" residual disease, providing key prognostic information and guiding necessary change of treatment.This paper provides an up-to-date overview of the WB-MRI and PET/CT techniques, their observations in responsive and progressive disease and their role and limitations in capturing minimal residual disease. It reviews trials assessing these techniques for response evaluation, points out the limited comparisons between both methods and highlights their complementarity with most recent molecular methods (next-generation flow cytometry, next-generation sequencing) to detect minimal residual disease. It underlines the important role of PET/MRI technology as a research tool to compare the effectiveness and complementarity of both methods to address the key clinical questions.


Assuntos
Mieloma Múltiplo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/terapia , Neoplasia Residual/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Imagem Corporal Total
11.
Lancet Oncol ; 22(3): e119-e130, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33545067

RESUMO

In this Policy Review, the Bone Working Group of the International Myeloma Working Group updates its clinical practice recommendations for the management of multiple myeloma-related bone disease. After assessing the available literature and grading recommendations using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method, experts from the working group recommend zoledronic acid as the preferred bone-targeted agent for patients with newly diagnosed multiple myeloma, with or without multiple myeloma-related bone disease. Once patients achieve a very good partial response or better, after receiving monthly zoledronic acid for at least 12 months, the treating physician can consider decreasing the frequency of or discontinuing zoledronic acid treatment. Denosumab can also be considered for the treatment of multiple myeloma-related bone disease, particularly in patients with renal impairment. Denosumab might prolong progression-free survival in patients with newly diagnosed multiple myeloma who have multiple myeloma-related bone disease and who are eligible for autologous stem-cell transplantation. Denosumab discontinuation is challenging due to the rebound effect. The Bone Working Group of the International Myeloma Working Group also found cement augmentation to be effective for painful vertebral compression fractures. Radiotherapy is recommended for uncontrolled pain, impeding or symptomatic spinal cord compression, or pathological fractures. Surgery should be used for the prevention and restoration of long-bone pathological fractures, vertebral column instability, and spinal cord compression with bone fragments within the spinal route.


Assuntos
Doenças Ósseas/tratamento farmacológico , Mieloma Múltiplo/complicações , Guias de Prática Clínica como Assunto/normas , Conservadores da Densidade Óssea , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Humanos
12.
Biol Blood Marrow Transplant ; 26(7): 1280-1287, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32194287

RESUMO

High-dose chemotherapy and autologous stem cell transplantation (ASCT) have provided effective treatment for patients with newly diagnosed multiple myeloma for more than 3 decades; however, which patients will benefit from tandem ASCT compared with single ASCT remains unclear. Here we retrospectively analyzed 978 trial and nontrial patients who underwent single or tandem ASCT in Heidelberg or other German-Speaking Myeloma Multicenter Group centers. Our results show that response improvement after first ASCT is a significant prognostic factor for progression-free survival benefit from tandem versus single ASCT (multivariable analysis, P = .002; hazard ratio, .64; 95% confidence interval, .48 to .85; P for interaction = .02). The depth of response after first ASCT and the cytogenetic profile did not have a significant prognostic effect on survival benefit from tandem ASCT. Our results suggest that it is not the response depth, but rather the response improvement after first ASCT is of prognostic significance regarding the benefit of tandem ASCT versus single ASCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
13.
Biol Blood Marrow Transplant ; 26(1): e7-e15, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31526843

RESUMO

The third annual Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was held on November 29, 2018, at the American Society of Hematology (ASH) annual meeting. This workshop featured the latest research focused on minimal residual disease (MRD) assessment and immune profiling (IP) in myeloma as well as discussion of the statistical and regulatory issues intrinsic to the development of MRD as a surrogate endpoint. In this report, we provide a summary of the workshop and focus on the integration of MRD and IP assessment into trial design and clinical practice.


Assuntos
Mieloma Múltiplo/terapia , Ensaios Clínicos como Assunto , Congressos como Assunto , Educação , Hematologia , Humanos , Mieloma Múltiplo/sangue , Neoplasia Residual , Sociedades Médicas , Estados Unidos
14.
Biol Blood Marrow Transplant ; 26(10): e247-e255, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32589921

RESUMO

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup has organized an annual workshop focused on minimal residual disease (MRD) testing and immune profiling (IP) in multiple myeloma since 2016. In 2019, the workshop took place as an American Society of Hematology (ASH) Friday Scientific Workshop titled "Immune Profiling and Minimal Residual Disease Testing in Multiple Myeloma." This workshop focused on 4 main topics: the molecular and immunologic evolution of plasma cell disorders, development of new laboratory- and imaging-based MRD assessment approaches, chimeric antigen receptor T cell therapy research, and statistical and regulatory issues associated with novel clinical endpoints. In this report, we provide a summary of the workshop and discuss future directions.


Assuntos
Mieloma Múltiplo , Medula Óssea , Humanos , Mieloma Múltiplo/terapia , Neoplasia Residual
15.
Blood ; 132(1): 59-66, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29784643

RESUMO

Spatial intratumor heterogeneity is frequently seen in multiple myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. Because biopsy-based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FLs) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches. Here, we investigated the prognostic value of FL size in 404 transplant-eligible, newly diagnosed MM patients. Using diffusion-weighted magnetic resonance imaging with background suppression, we identified the presence of multiple large FLs as a strong prognostic factor. Patients with at least 3 large FLs with a product of the perpendicular diameters >5 cm2 were associated with poor progression-free survival (PFS) and overall survival (OS; median, 2.3 and 3.6 years, respectively). This pattern, seen in 13.8% of patients, was independent of the Revised International Staging System (RISS), gene expression profiling (GEP)-based risk score, gain(1q), or extramedullary disease (hazard ratio, 2.7 and 2.2 for PFS and OS in multivariate analysis, respectively). The number of FLs lost its negative impact on outcome after adjusting for FL size. In conclusion, the presence of at least 3 large FL is a feature of high risk, which can be used to refine the diagnosis of this type of disease behavior and as an entry criterion for risk-stratified trials.


Assuntos
Imagem de Difusão por Ressonância Magnética , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/mortalidade , Adulto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Taxa de Sobrevida
16.
J Natl Compr Canc Netw ; 18(12): 1685-1717, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33285522

RESUMO

Multiple myeloma is a malignant neoplasm of plasma cells that accumulate in bone marrow, leading to bone destruction and marrow failure. This manuscript discusses the management of patients with solitary plasmacytoma, smoldering multiple myeloma, and newly diagnosed multiple myeloma.


Assuntos
Mieloma Múltiplo , Medula Óssea , Humanos , Oncologia , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Plasmócitos , Plasmocitoma
17.
Lancet Oncol ; 20(6): e302-e312, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31162104

RESUMO

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.


Assuntos
Diagnóstico por Imagem/métodos , Imagem Multimodal/métodos , Mieloma Múltiplo/diagnóstico , Paraproteinemias/diagnóstico , Plasmócitos/patologia , Guias de Prática Clínica como Assunto/normas , Consenso , Humanos , Agências Internacionais , Mieloma Múltiplo/diagnóstico por imagem , Paraproteinemias/diagnóstico por imagem
18.
Biol Blood Marrow Transplant ; 25(3): e89-e97, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30408566

RESUMO

The second annual Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was convened on December 7, 2017, at the American Society of Hematology (ASH) meeting. During this workshop, investigators from around the world presented their latest research involving assessment of minimal residual disease (MRD) and immune profiling (IP) in myeloma. This document summarizes the workshop presentations as well as relevant ASH abstracts and focuses on the regulatory issues involved in the integration of MRD and IP assessment in clinical trial design and practice.


Assuntos
Transplante de Medula Óssea , Congressos como Assunto , Educação , Fatores Imunológicos , Mieloma Múltiplo/patologia , Neoplasia Residual , Transplante de Medula Óssea/educação , Ensaios Clínicos como Assunto , Humanos , Sociedades Científicas
19.
Radiology ; 291(1): 5-13, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30806604

RESUMO

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.


Assuntos
Mieloma Múltiplo/diagnóstico , Guias de Prática Clínica como Assunto , Consenso , Coleta de Dados , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Projetos de Pesquisa , Imagem Corporal Total/métodos , Imagem Corporal Total/normas
20.
NMR Biomed ; 32(9): e4122, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31206946

RESUMO

Multiple myeloma (MM) is a largely incurable, debilitating hematologic malignancy of terminally differentiated plasma cells in the bone marrow (BM). Identification of therapeutic response is critical for improving outcomes and minimizing costs and off-target toxicities. To assess changes in BM environmental factors and therapy efficacy, there is a need for noninvasive, nonionizing, longitudinal, preclinical methods. Here, we demonstrate the feasibility of preclinical magnetic resonance imaging (MRI) for longitudinal imaging of diffuse tumor burden in a syngeneic, immunocompetent model of intramedullary MM. C57Bl/KaLwRij mice were implanted intravenously with 5TGM1-GFP tumors and treated with a proteasome inhibitor, bortezomib, or vehicle control. MRI was performed weekly with a Helmholtz radiofrequency coil placed on the hind leg. Mean normalized T1-weighted signal intensities and T2 relaxation times were quantified for each animal following manual delineation of BM regions in the femur and tibia. Finally, tumor burden was quantified for each tissue using hematoxylin and eosin staining. Changes in T2 relaxation times correlated strongly to cell density and overall tumor burden in the BM. Median T2 relaxation times and regional T1-weighted contrast uptake were shown to be most relevant in identifying posttherapy disease stage in this model of intramedullary MM. In summary, our results highlighted potential preclinical MRI markers for assessing tumor burden and BM heterogeneity following bortezomib therapy, and demonstrated the application of longitudinal imaging with preclinical MRI in an immunocompetent, intramedullary setting.


Assuntos
Bortezomib/uso terapêutico , Imageamento por Ressonância Magnética , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/tratamento farmacológico , Carga Tumoral , Animais , Biomarcadores/metabolismo , Medula Óssea/patologia , Meios de Contraste/química , Fêmur/diagnóstico por imagem , Fêmur/patologia , Camundongos Endogâmicos C57BL , Mieloma Múltiplo/patologia , Reprodutibilidade dos Testes , Tíbia/diagnóstico por imagem , Tíbia/patologia
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