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The treatment of newly diagnosed multiple myeloma has changed dramatically over the past 20 years, from near uniform application of chemotherapy to a patient performance status- and risk-based approach. Furthermore, initiation of ...
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The treatment of newly diagnosed multiple myeloma has changed dramatically over the past 20 years, from near uniform application of chemotherapy to a patient performance status- and risk-based approach. Furthermore, initiation of treatment criteria have evolved from a pure end-organ damage-based definition to include risk factors of transformation to frank myeloma. Besides, the mainly cytogenetically defined Multiple Myeloma (MM) risk status, transplant eligibility of patients still serves primarily to allocate patients within a rational treatment algorithm. While all transplant-eligible MM patients should receive a triplet induction therapy followed by autolo-gous transplantation and, in most cases, lenalidomide maintenance, other therapeutic elements (e. g., other maintenance strategies, consolidation, tandem transplantation,..) have to be decided on an individualized appraisal of risk and toxicities. Standard-risk patients should never be undertreated, as they derive the highest relative benefit from using the best available registered therapies. However, high-risk patients should be preferentially treated inside clinical trials testing additive innovative treatments, as the improvement in the prognosis of this group of patients by standard therapies has been underwhelming. Furthermore, the evaluation process of non-transplant-eligible patients should always comprise an evaluation of performance status, frailty, and comorbidities (e. g., a comprehensive geriatric assessment) to facilitate the allocation of individualized therapies.
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Multiple myeloma(MM) is an incurable plasma cell malignancy. Despite an improvement in OS over the past 2 decades, most patients do experience disease relapse. A subset of patients who experience an early disease relapse within 1-...
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Multiple myeloma(MM) is an incurable plasma cell malignancy. Despite an improvement in OS over the past 2 decades, most patients do experience disease relapse. A subset of patients who experience an early disease relapse within 1-2 years post-transplant, and considered functional high-risk. Recent findings implicated high-risk cytogenetic features and minimal residual disease as negative prognostic factors, each independently associated with early relapse among autologous stem cell transplant recipients(ASCT). The spectrum of disease relapse could range from asymptomatic/biochemical to more aggressive forms such as plasma cell leukemia. Hence, it is imperative that therapy be tailored based on these patterns of relapse upon presentation. The past few years have witnessed an explosion in the armamentarium of second-line agents for the treatment of relapsed MM. Accordingly, choosing the optimal regimen has become quite challenging for the practicing clinician. In this review, we outline the approach for therapy selection, which takes into account underlying comorbid conditions, duration of response, presence of high-risk features, etc Due to a better understanding of disease biology coupled with the advances in molecular techniques, the treatment landscape of relapsed MM (posttransplant) will most likely continue to evolve. Novel agents with distinct modes of action, such as immune therapies and novel oral agents are undergoing investigation in the relapsed setting. Once approved, these agents could potentially alter the course of the disease and possibly challenge the role of ASCT.
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We read with interest the data from Grey-Davies et al, which demonstrates the activity of the combination of bendamustine, thalidomide and dexamethasone in a proportion of multiply relapsed cohort of myeloma patients. We have prev...
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We read with interest the data from Grey-Davies et al, which demonstrates the activity of the combination of bendamustine, thalidomide and dexamethasone in a proportion of multiply relapsed cohort of myeloma patients. We have previously published the safety and activity of this combination in myeloma patients with renal impairment (Ramasamy et al, 2011). However, the optimal dose of bendamustine in combination with thalidomide and dexamethasone is yet to be denned. We used a fixed dose of 120 mg of bendamustine per cycle, which was tolerated well, with Grade 3/4 haemato-logical toxicity in two out of nine patients. In this heavily pre-treated cohort with pre-existing cytopenias, 39% emergent Grade 3/4 haematological toxicity was observed at a cumulative median bendamustine dose of 390 mg/m2. We hope the current Myeloma UK (MUK one) trial, a Phase II randomized bendamustine dose-finding study in combination with thalidomide and dexamethasone, will shed light on a dosing strategy.
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Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or m...
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Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), and traditional dogma dictates that treatment should be initiated on frank MM symptom development. Emerging evidence suggests that a defined group of "high-risk SMM" may benefit from early treatment, before organ damage and symptoms actually occur. The following article frames the evidence for treatment of high-risk SMM by defining risk categories, reviewing existing therapeutic trial data, and exploring the long-term biologic implications of early treatment. (C) 2016 Elsevier Inc. All rights reserved.
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Summary 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 ...
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Summary 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.
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This cohort study assesses the concordance of 3 models to stratify risk for progression to multiple myeloma in an independent cohort of patients with smoldering multiple myeloma.
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The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown cli...
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The treatment of multiple myeloma has evolved markedly in the last decade, but mortality remains high, emphasizing the need for more effective therapies. Daratumumab, a fully human monoclonal antibody targeting CD38, has shown clinical efficacy in relapsed/ refractory multiple myeloma both as monotherapy and in combination with other drugs, including novel agents. More recently, promising results have been reported in patients with untreated newly diagnosed multiple myeloma (NDMM). Clinical trials thus far have shown enhanced efficacy and tolerability of several daratumumab-based combinations in both transplant ineligible and eligible patients, without compromising transplant ability. However, benefit in high-risk subpopulations is still unclear. A subcutaneous formulation of daratumumab has been introduced to decrease the risk of infusion reactions, with preliminary results showing non-inferior efficacy. The antimyeloma activity of daratumumab is achieved through multiple mechanisms including direct, Fc-dependent, and immunomodulatory mechanisms. Enhanced efficacy of daratumumab in combination with immunomodulatory drugs and proteasome inhibitors is supported by preclinical data showing synergism. This review will focus on the role of daratumumab in untreated NDMM patients, highlighting the results of major clinical trials, and listing ongoing trials that are evaluating various daratumumab-based combinations in this setting.
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