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American Society of Clinical Oncology... Apr 2022Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple...
Historically, multiple myeloma has been considered an incurable disease, mainly because of its recurrence after transient control. However, the landscape of multiple myeloma therapeutics has significantly changed over the last 2 decades, with disease remissions lasting much longer. The advent of modern-day induction regimens, usage of high-dose melphalan followed by autologous stem cell transplantation, and well-tolerated maintenance regimens has resulted in deeper and durable responses, with less frequent disease recurrences, and patients are living much longer. Moreover, the conventional testing for response assessments in multiple myeloma was developed at least 60 years earlier, and there was a clear need for more sensitive diagnostics to test measurable residual disease at deeper levels. Next-generation sequencing and next-generation flow cytometry are highly sensitive techniques that were refined over the last decade and have a sensitivity of 10 to 10 (1 cell per 100,000/1 million). More recently, immunotherapy strategies-including the cellular therapies-have allowed us to expand our ability to achieve and maintain measurable residual disease negativity even in the refractory setting. These advances have brought us much closer to a cure for multiple myeloma; clearly, it has become more realistically achievable, challenging the dogma of multiple myeloma as an incurable disease.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm, Residual; Transplantation, Autologous
PubMed: 35623025
DOI: 10.1200/EDBK_349603 -
Blood Feb 2019Bone disease is the most frequent feature of multiple myeloma (MM) and represents a marker of end-organ damage; it is used to establish the diagnosis and to dictate the... (Review)
Review
Bone disease is the most frequent feature of multiple myeloma (MM) and represents a marker of end-organ damage; it is used to establish the diagnosis and to dictate the immediate need for therapy. For this reason, imaging plays a significant role in the management of MM patients. Although conventional radiography has traditionally been the standard imaging modality, its low sensitivity in detecting osteolytic lesions and inability to evaluate response to therapy has called for the use of more sophisticated techniques, such as whole-body low-dose computed tomography (WBLDCT), whole-body magnetic resonance imaging, and F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT). In this review, the advantages, indications of use, and applications of the 3 techniques in the management of patients with MM in different settings will be discussed. The European Myeloma Network and the European Society for Medical Oncology guidelines have recommended WBLDCT as the imaging modality of choice for the initial assessment of MM-related lytic bone lesions. Magnetic resonance imaging is the gold-standard imaging modality for detection of bone marrow involvement, whereas PET/CT provides valuable prognostic data and is the preferred technique for assessment of response to therapy. Standardization of most of the techniques is ongoing.
Topics: Humans; Multiple Myeloma; Prognosis; Whole Body Imaging
PubMed: 30587527
DOI: 10.1182/blood-2018-08-825356 -
Expert Review of Hematology Feb 2014Multiple myeloma (MM) is a heterogeneous disease that, over the past 15 years, has seen an increased understanding of its biology and of novel therapeutic options.... (Review)
Review
Multiple myeloma (MM) is a heterogeneous disease that, over the past 15 years, has seen an increased understanding of its biology and of novel therapeutic options. Distinctive subtypes of the disease have been described, each with different outcomes and clinic-pathological features. Even though a detailed classification of MM into at least seven or eight major subtypes is possible, a more practical clinical approach can classify the disease into high-risk and non-high-risk MM. Such classification has permitted a more personalized approach to the management of the disease. Additionally, risk stratification should be included in outcome discussions with patients, as survival differs significantly by high-risk status. Nowadays, test for risk stratification are widely available and can be routinely used in the clinic. A greater understanding of the genetic abnormalities underlying the biology of MM will allow for the development of novel targeted therapies and better prognostic markers of the disease.
Topics: Biomarkers; Chromosome Aberrations; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Immunologic Factors; Multiple Myeloma; Neoplasm, Residual; Prognosis; Protease Inhibitors; Stem Cell Transplantation
PubMed: 24483346
DOI: 10.1586/17474086.2014.882224 -
American Society of Clinical Oncology... May 2018Major advances have occurred in the treatment of multiple myeloma, including several new drugs that typically cost more than $100,000 per year. Although the gains in... (Review)
Review
Major advances have occurred in the treatment of multiple myeloma, including several new drugs that typically cost more than $100,000 per year. Although the gains in myeloma therapy improve overall survival considerably, they are available to only a fraction of the population of patients with myeloma in the world because of regulatory barriers and cost. Myeloma is an example of what is happening in cancer on a much larger scale. Many of the problems discussed call for a wider discussion across all cancers, but they are amplified in myeloma because of the need for multidrug regimens that combine three or more expensive new drugs for prolonged periods of time. In this article, the reasons for the high cost of cancer drugs and possible solutions are examined. The lack of correlation of value and price, the remarkable rise in prices of existing old medications over time, and the lack of access to lifesaving drugs across various countries are also discussed.
Topics: Humans; Multiple Myeloma
PubMed: 30231405
DOI: 10.1200/EDBK_200867 -
TheScientificWorldJournal 2013Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM.... (Review)
Review
Multiple myeloma (MM) has a high incidence rate in the elderly. Responsiveness to treatments differs considerably among patients because of high heterogeneity of MM. Chronic kidney disease (CKD) is a common clinical feature in MM patients, and treatment-related mortality and morbidity are higher in MM patients with CKD than in patients with normal renal function. Recent advances in diagnostic tests, chemotherapy agents, and dialysis techniques are providing clinicians with novel approaches for the management of MM patients with CKD. Once reversible factors, such as hypercalcemia, have been corrected, the most common cause of severe acute kidney injury (AKI) in MM patients is tubulointerstitial nephropathy, which results from very high circulating concentrations of monoclonal immunoglobulin free light chains (FLC). In the setting of AKI, an early reduction of serum FLC concentration is related to kidney function recovery. The combination of extended high cutoff hemodialysis and chemotherapy results in sustained reductions in serum FLC concentration in the majority of patients and a high rate of independence from dialysis.
Topics: Humans; Multiple Myeloma; Renal Insufficiency, Chronic
PubMed: 24288486
DOI: 10.1155/2013/487285 -
British Journal of Haematology Oct 2015In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple...
In November 2014 the International Myeloma Working Group (IMWG) revised the definition of multiple myeloma, such that asymptomatic patients with newly diagnosed multiple myeloma without any of the traditional 'CRAB' (hypercalcaemia, renal impairment, anaemia, bone disease) end organ damage criteria but with one of three new criteria would be recommended to start treatment. Previously, the standard of care for such patients was expectant management. These three new criteria are: greater than 60% clonal plasma cells on bone marrow biopsy, a serum free light chain (sFLC) ratio of >100 (the involved sFLC must be >100 mg/l) and greater than one unequivocal focal lesion on advanced imaging (low dose whole body computerized tomography, magnetic resonance imaging, (18) F fluorodeoxyglucose positron emission tomography). Although this would appear to affect a small number of patients, the impact of these changes are broad, leading to an increased use of advanced imaging, a debate around the management of patients previously diagnosed with smouldering myeloma, changed terminology and clinical trial design and an extension of the use of biomarkers. For the first time the philosophy of treatment in myeloma will change from treatment initiation only being triggered by overt end organ damage to an era where sub clinical risk factors will also be taken into account.
Topics: Biomarkers, Tumor; Humans; Multiple Myeloma; Radiography
PubMed: 26221971
DOI: 10.1111/bjh.13620 -
Haematologica Mar 2017Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer. Multiple myeloma represents a genuine example of disrupted immune... (Review)
Review
Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer. Multiple myeloma represents a genuine example of disrupted immune surveillance characterized by: impaired antibody production, deregulation of the T and natural killer cell compartment, disruption of antigen presentation machinery, upregulation of inhibitory surface ligands, and recruitment of immunosuppressive cells. Although the potential value of immunotherapeutic interventions had a clear antecedent in the graft--myeloma effect induced by allogeneic stem cell transplant and donor lymphocyte infusions, it is only recently that this field has faced a real revolution. In this review we discuss the current results obtained with immune approaches in patients with multiple myeloma that have placed this disease under the scope of immuno-oncology, bringing new therapeutic opportunities for the treatment of multiple myeloma patients.
Topics: Animals; Antigens, Neoplasm; Cancer Vaccines; Combined Modality Therapy; Humans; Immune Evasion; Immunologic Surveillance; Immunotherapy; Molecular Targeted Therapy; Multiple Myeloma
PubMed: 28082344
DOI: 10.3324/haematol.2016.152504 -
Haematologica Jul 2020Central nervous system involvement in multiple myeloma is a rare complication but carries a very poor prognosis. We provide a review of current literature, including... (Review)
Review
Central nervous system involvement in multiple myeloma is a rare complication but carries a very poor prognosis. We provide a review of current literature, including presentation, treatment and survival data, and describe our experience in a regional hematologic malignancy diagnosis center where, over a 15-year period, ten cases were identified. Although the median age of onset, frequently between 50-60 years, is comparatively young, those diagnosed usually have a preceding diagnosis of multiple myeloma and often have had several lines of treatment. We discuss putative underlying factors such as prior treatment and associations including possible risk factors and features suggestive of a distinct biology. Central nervous system involvement may be challenging to diagnose in myeloma, displaying heterogeneous symptoms that can be confounded by neurological symptoms caused by the typical features of myeloma or treatment side-effects. We discuss the clinical features, imaging and laboratory methods used in diagnosis, and highlight the importance of considering this rare complication when neurological symptoms occur at presentation or, more commonly, during the disease pathway. In the absence of clinical trial data to inform an evidence-based approach to treatment, we discuss current and novel treatment options. Finally, we propose the establishment of an International Registry of such cases as the best way to collect and subsequently disseminate presentation, diagnostic and treatment outcome data on this rare complication of multiple myeloma.
Topics: Central Nervous System; Humans; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Prognosis; Registries
PubMed: 32414852
DOI: 10.3324/haematol.2020.248518 -
Hematology/oncology and Stem Cell... Dec 2017There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients.... (Review)
Review
There have been major recent advancements in the understanding and management of multiple myeloma which in turn has led to unprecedented survival outcomes for patients. Diagnostic and response criteria have been recently revised. Our understanding of clonal progression, evolution, and clonal tides will inform therapeutic choices and appropriate treatment for patients. Response rates to initial induction with modern triplet therapies containing proteasome inhibitors and immunomodulators have made this approach the global standard for initial treatment. Although the relevance of autologous transplantation has been questioned in the setting of modern induction therapy, we have new data suggesting its continued relevance. Recent studies performed in the context of novel agent induction suggest that autologous transplantation continues to improve response rates and progression-free survival, thus underscoring its role in transplant-eligible patients. Emerging paradigms in the treatment of multiple myeloma include immune approaches, such as adoptive cellular therapies, vaccines, or antibody-based immune manipulations, all of which seem to synergize with a transplant platform. Allogeneic transplantation is limited in scope by the concern of prohibitive toxicity and is applicable mainly to younger patients with high-risk disease. However, the allogeneic approach offers even more options of immunotherapy at relapse, including donor lymphocyte infusions, immunomodulatory drug maintenance, and withdrawal of immune suppression.
Topics: Adoptive Transfer; Allografts; Antineoplastic Agents, Immunological; Autografts; Cancer Vaccines; Hematopoietic Stem Cell Transplantation; Humans; Immunologic Factors; Multiple Myeloma
PubMed: 28633036
DOI: 10.1016/j.hemonc.2017.05.005 -
Cytokine & Growth Factor Reviews Apr 2024Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully... (Review)
Review
Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully utilise the antitumour potential of immune cells. T and NK cell-derived immune lymphocytes both expressed activating NK receptor group 2 member D(NKG2D). This receptor can identify eight distinct NKG2D ligands (NKG2DL), including major histocompatibility complex class I (MHC) chain-related protein A and B (MICA and MICB). Their binding to NKG2D triggers effector roles in T and NK cells. NKG2DL is polymorphic in MM cells. The decreased expression of NKG2DL on the cell surface is explained by multiple mechanisms of tumour immune escape. In this review, we discuss the mechanisms by which the NKG2D/NKG2DL axis regulates immune effector cells and strategies for promoting NKG2DL expression and inhibiting its release in multiple myeloma and propose therapeutic strategies that increase the expression of NKG2DL in MM cells while enhancing the activation and killing function of NK cells.
Topics: Humans; Multiple Myeloma; NK Cell Lectin-Like Receptor Subfamily K; Killer Cells, Natural; Histocompatibility Antigens Class I; Immunotherapy
PubMed: 38378397
DOI: 10.1016/j.cytogfr.2024.02.001