MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

A virtual approach to evaluate therapies for management of multiple myeloma induced bone disease: Modelling Therapies for Multiple Myeloma Induced Bone Disease

Multiple myeloma bone disease is devastating for patients and a major cause of morbidity. The disease leads to bone destruction by inhibiting osteoblast activity while stimulating osteoclast activity. Recent advances in multiple myeloma research have improved our understanding of the pathogenesis of multiple myeloma-induced bone disease and suggest several potential therapeutic strategies. However, the effectiveness of some potential therapeutic strategies still requires further investigation and optimization. In this paper, a recently developed mathematical model is extended to mimic and then evaluate three therapies of the disease, namely: bisphosphonates, bortezomib and TGF-β inhibition. The model suggests that bisphosphonates and bortezomib treatments not only inhibit bone destruction, but also reduce the viability of myeloma cells. This contributes to the current debate as to whether bisphosphonate therapy has an anti-tumour effect. On the other hand, the analyses indicate that treatments designed to inhibit TGF-β do not reduce bone destruction, although it appears that they might reduce the viability of myeloma cells, which again contributes to the current controversy regarding the efficacy of TGF-β inhibition in multiple myeloma-induced bone disease

Myelomatous Pleural Effusion

ABSTRACT Multiple myeloma (MM) is a common hematologic malignancy. Pleural effusion is a rare presenting feature of multiple myeloma which carries a poor prognosis. Few cases of multiple myeloma with pleural involvement have been reported in the medical literature. We report a patient with MM diagnosed by cytologic examination of pleural fluid. Our patient was a 64- year old man with multiple myeloma who was receiving chemotherapy. He had developed dry coughs and exertional dyspnea about a month prior to the admission. Radiographic examination showed left pleural effusion with mediastinal shift to the opposite side. Diagnostic thoracentesis of pleural fluid was performed for the patient. Pathologic examination of pleural fluid showed plasmocytes and plasmablast type mononuclear cells with atypical nuclei, consistent with the diagnosis of pleural effusion due to multiple myeloma. In view of multiple etiologies of pleural effusion in malignant diseases, rare etiologies should also be considered in order to treat the effusion appropriately. (Tanaffos 2007; 6(2): 68-72) Key words: Multiple myeloma, Pleural effusion, Plasmablas

Incidence and Risk Factors of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients Having Undergone Autologous Stem Cell Transplantation

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy. Due to their long survival and subsequently high cumulative doses of bisphosphonates, multiple myeloma patients have the highest risk of developing BRONJ of all patients treated with bisphosphonates. The purpose of the present study was to evaluate the incidence and risk factors for BRONJ in multiple myeloma patients after high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients and Methods: We retrospectively analyzed the data of 120 multiple myeloma patients after high-dose chemotherapy and ASCT treated with bisphosphonates and assessed the incidence and risk factors of BRONJ. Results: Of the 120 patients, 23 (19%) developed BRONJ. 6 patients suffered several BRONJ events, resulting in a total incidence of 23%. The risk for BRONJ was significantly higher for patients with rheumatism and recent dental manipulations. Furthermore, the number of previous bisphosphonate rotations, the duration of bisphosphonate therapy, and the type and cumulative dose of bisphosphonate used were associated with the incidence of BRONJ. Conclusion: Our study is the first to determine the risk of BRONJ in a homogeneous group of multiple myeloma patients treated with high-dose chemotherapy and ASCT

Multiple myeloma and physical activity: a scoping review

Objectives: Multiple myeloma is the second most common haematological cancer. A growing body of literature is emerging that investigates the role physical activity plays in all stages of multiple myeloma (prevention and survivorship) and to date no attempt has been made to collate and understand this literature. Therefore, this scoping review aims to (1) outline what is already known about physical activity in all stages of multiple myeloma (2) map the literature on physical activity and multiple myeloma and (3) identify future directions for research. Design: Scoping Review. Data Sources: Searches were carried out in May 2015. Searches were conducted in PubMed, Web of Science, SPORTdiscus and MEDLINE. Eligibility criteria for selecting studies: To be included studies had to report original data, investigate physical activity per se or physical activity correlates and multiple myeloma or smouldering multiple myeloma. Results: A total of 19 papers received full screening, 5 of these papers were excluded. This review identified three journal articles relating to the role of physical activity in the prevention of multiple myeloma, nine papers were identified in the treatment of multiple myeloma and two on smouldering multiple myeloma. Conclusions: The search identified that the literature surrounding multiple myeloma and physical activity is very limited. We encourage those designing new cohort studies to allow for future assessment of associations between physical activity and onset of multiple myeloma and smouldering multiple myeloma, as well as the potential role that physical activity plays in the progression from smouldering multiple myeloma to multiple myeloma. Second, we encourage the design and investigation of gender and treatment-specific physical activity interventions in patients with multiple myeloma. Finally, we highlight the need for more randomised controlled trials to evaluate the impact of different types, frequencies and intensities of physical activity on various health parameters in multiple myeloma survivors

Multiple Myeloma : an update on disease biology and therapy

Multiple myeloma is a malignancy of immunoglobulin producing plasma cells. Clinical features include bone pain due to lytic bone lesions or pathological fractures, anemia, symptomatic hypercalcemia, renal insufficiency, recurrent infections and amyloidosis. In the last few years, there have been considerable advances in the understanding of the biology of this disease. While multiple myeloma is biologically diverse, several oncogenes are activated in this illness. In addition, the role of the bone marrow microenvironment to support the growth and survival of the malignant cells has been well described. In this review, we discuss recent developments in the molecular pathogenesis of myeloma. These recent observations are being translated into novel therapeutic approaches that target both the tumor cell as well as the stroma. Current therapeutic strategies are discussed.peer-reviewe

MICA Expressed by Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Plasma Cells Costimulates Pamidronate-Activated γδ Lymphocytes

Abstract Amino-biphosphonates (like pamidronate) activate human Vγ9/Vδ2 T lymphocytes and promote their cytotoxicity against multiple myeloma cells. T-cell receptor (TCR)–mediated effector functions of γδ cells are enhanced upon triggering of the activating receptor NKG2D by MICA, a stress-inducible antigen expressed by epithelial and some hematopoietic tumors, including multiple myeloma. Here we show that MICA was expressed not only by myeloma cell lines and by 6 of 10 primary multiple myeloma cells from patients but also by bone marrow plasma cells from all (six of six) patients with preneoplastic gammopathy (monoclonal gammopathy of undetermined significance, MGUS), a direct precursor of multiple myeloma. Moreover, compared with multiple myeloma plasma cells, MICA was expressed by MGUS plasma cells at significantly (P < 0.05) higher levels. MICA expressed by myeloma cell lines contributed to killing and IFN-γ production by Vγ9/Vδ2 cells only upon pamidronate treatment, suggesting a dual interaction between Vγ9/Vδ2 lymphocytes and multiple myeloma plasma cells involving both TCR triggering and NKG2D-mediated signals. Finally, MICA enhanced killing of freshly derived, pamidronate-treated multiple myeloma cells from patients by γδ cells, as indicated by the significantly (P < 0.05) higher γδ cytotoxicity against MICA-positive rather than MICA-negative multiple myeloma cells. Our results indicate that MICA expressed by monoclonal plasma cells is functional and correlates with disease stages, suggesting a role for the molecule in the immune surveillance against multiple myeloma. Moreover, pamidronate-activated Vγ9/Vδ2 lymphocytes can be exploited in the immune therapy of early stages multiple myeloma and possibly of premalignant disease

Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study

BackgroundMultiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time. We aimed to identify how MGUS and multiple myeloma plasma cell clones responded to anti-multiple myeloma therapy in patients newly diagnosed with biclonal gammopathy multiple myeloma.MethodsIn this retrospective cohort study, we identified patients with biclonal gammopathy multiple myeloma by central laboratory analysis of 6399 newly diagnosed patients with multiple myeloma enrolled in three UK clinical trials (Myeloma IX, Myeloma XI, and TEAMM) between July 7, 2004, and June 2, 2015. In addition to the inclusion criteria of these trials, our study necessitated at trial entry the presence of two distinct M proteins in immunofixation electrophoresis. The primary endpoint was difference in response achieved with anti-multiple myeloma therapy on MGUS (which we defined as M2) and multiple myeloma (M1) clones—overall, within patients, and between therapy types—with international therapy response criteria assessed with χ2 analyses. We analysed by intention to treat.Findings44 patients with biclonal gammopathy multiple myeloma with IgG or IgA MGUS clones were subsequently identified from the three trials and then longitudinally monitored. 41 (93%) of M1 clones had a response to therapy (either complete response, very good partial response, partial response, or minor response) compared with only 28 (64%) of M2 clones (p=0·0010). For the 20 patients who received intensive therapy, there was no difference between the proportion of responding clones in M1 (19 [95%]) and M2 (15 [75%], p=0·13). However, for the 17 patients who received non-intensive therapy, 16 (94%) of M1 clones had a response compared with ten [59%] of M2 clones (p=0·031). When examining clones within the same patient, 30 (68%) of 44 individual patients had different levels of responses within the M1 and M2 clones. One patient exhibited M2 progression to myeloma and subsequently died.InterpretationThese results show that, in patients with biclonal gammopathy multiple myeloma, anti-multiple myeloma therapies exert a greater depth of response against multiple myeloma plasma cell clones than MGUS plasma cell clones. Although some MGUS clones exhibited a complete response, many did not respond, which suggests that the underlying features that render multiple myeloma plasma cells susceptible to therapy are present in only some MGUS plasma cell clones. To determine MGUS clone susceptibly to therapy, future studies might seek to identify, with biclonal gammopathy multiple myeloma as an investigative model, the genetic and epigenetic alterations that affect whether MGUS plasma cell clones are responsive to anti-multiple myeloma therapy