-
Blood Jul 2023
Topics: Humans; Multiple Myeloma; Eligibility Determination; Ethnicity
PubMed: 37471108
DOI: 10.1182/blood.2023020327 -
Journal of Nuclear Medicine : Official... Sep 2023Recent innovative strategies have dramatically redefined the therapeutic landscape for treating multiple myeloma patients. In particular, the development and application...
Recent innovative strategies have dramatically redefined the therapeutic landscape for treating multiple myeloma patients. In particular, the development and application of immunotherapy and high-dose therapy have demonstrated high response rates and have prolonged remission duration. Over the past decade, new morphologic or hybrid imaging techniques have gradually replaced conventional skeletal surveys. PET/CT using F-FDG is a powerful imaging tool for the workup at diagnosis and for therapeutic evaluation allowing medullary and extramedullary assessment. The independent negative prognostic value for progression-free and overall survival derived from baseline PET-derived parameters such as the presence of extramedullary disease or paramedullary disease, as well as the number of focal bone lesions and SUV, has been reported in several large prospective studies. During therapeutic evaluation, F-FDG PET/CT is considered the reference imaging technique because it can be performed much earlier than MRI, which lacks specificity. Persistence of significant abnormal F-FDG uptake after therapy is an independent negative prognostic factor, and F-FDG PET/CT and medullary flow cytometry are complementary tools for detecting minimal residual disease before maintenance therapy. The definition of a PET metabolic complete response has recently been standardized and the interpretation criteria harmonized. The development of advanced PET analysis and radiomics using machine learning, as well as hybrid imaging with PET/MRI, offers new perspectives for multiple myeloma imaging. Most recently, innovative radiopharmaceuticals such as C-X-C chemokine receptor type 4-targeted small molecules and anti-CD38 radiolabeled antibodies have shown promising results for tumor phenotype imaging and as potential theranostics.
Topics: Humans; Multiple Myeloma; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Prospective Studies; Immunotherapy
PubMed: 37591548
DOI: 10.2967/jnumed.122.264972 -
American Journal of Hematology Feb 2024Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in...
DISEASE OVERVIEW
Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS."
DIAGNOSIS
Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.
PROGNOSIS
N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively.
THERAPY
All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.
FUTURE CHALLENGES
Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Prognosis; Immunoglobulin Light Chains; Hematopoietic Stem Cell Transplantation
PubMed: 38095141
DOI: 10.1002/ajh.27177 -
Brain and Nerve = Shinkei Kenkyu No... May 2024AL amyloidosis, derived from amyloidogenic immunoglobulin light chains, is a common type of systemic amyloidosis. Peripheral neuropathy has been identified in 10%-40% of... (Review)
Review
AL amyloidosis, derived from amyloidogenic immunoglobulin light chains, is a common type of systemic amyloidosis. Peripheral neuropathy has been identified in 10%-40% of patients with systemic AL amyloidosis. Definitive diagnosis requires tissue biopsies, including skin, fat, and gastrointestinal samples, as well as amyloid typing. Disease-modifying therapies have been shown to improve patient survival and prevent progressive organ dysfunction.
Topics: Humans; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin Light Chains
PubMed: 38741500
DOI: 10.11477/mf.1416202647 -
Hematology/oncology Clinics of North... Apr 2024Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal... (Review)
Review
Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hyperdiploidy. Subsequent loss of function of tumor suppressor genes and mutations activating MYC, RAS, NFkB, and cell cycle pathways are associated with the progression to malignant disease.
Topics: Humans; Multiple Myeloma; Translocation, Genetic; Gene Rearrangement; Mutation; Monoclonal Gammopathy of Undetermined Significance; Immunoglobulins
PubMed: 38199896
DOI: 10.1016/j.hoc.2023.12.010 -
Hematology/oncology Clinics of North... Apr 2024Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic... (Review)
Review
Improving the outcome of high-risk myeloma (HRMM) is a key therapeutic aim for the next decade. To achieve this aim, it is necessary to understand in detail the genetic drivers underlying this clinical behavior and to target its biology therapeutically. Advances have already been made, with a focus on consensus guidance and the application of novel immunotherapeutic approaches. Cases of HRMM are likely to have impaired prognosis even with novel strategies. However, if disease eradication and minimal disease states are achieved, then cure may be possible.
Topics: Humans; Multiple Myeloma; Prognosis
PubMed: 38195306
DOI: 10.1016/j.hoc.2023.12.008 -
Ophthalmic Plastic and Reconstructive...To characterize clinical and radiographic features, management, and outcomes of patients with orbital involvement of multiple myeloma (MM). (Review)
Review
PURPOSE
To characterize clinical and radiographic features, management, and outcomes of patients with orbital involvement of multiple myeloma (MM).
METHODS
A retrospective chart review identified patients with MM and orbital involvement confirmed by histopathology at a single institution between 1995 and 2021. A comprehensive literature review was performed via PubMed to identify all previously reported cases of orbital MM.
RESULTS
Retrospective review identified 7 patients (43% male, mean age 68.7 years). Presenting symptoms included proptosis and diplopia. Orbital lesions were primarily located laterally (42.8%) with associated extraocular muscle (57.1%) or lacrimal gland (42.9%) involvement. Five patients (71.4%) had a previous diagnosis of systemic MM. Six patients received chemoradiation (85.7%). All patients had improvement of orbital disease with 2 patients deceased due to disease at follow-up (mean 8.9 months). Literature review identified 111 cases (46.8% male, mean age 58.6 years). 48.6% presented with orbital disease as the first manifestation of systemic MM. Lesions were most commonly located superolaterally (20.2%) with extraocular muscle infiltration (25.2%), lacrimal gland involvement (7.2%), and orbital bony destruction (39.6%). Treatments included chemoradiation, chemotherapy, or radiation alone. Approximately half (51.4%) of patients experienced improvement in orbital disease following treatment, and 48.6% were deceased at follow-up (mean 20.1 months).
CONCLUSIONS
This study provides a new retrospective study and updated comprehensive literature review regarding orbital MM. Given its poor prognosis, characterization of orbital MM is essential for early diagnosis. Orbital MM is often unilateral, located superolaterally, and may represent the first manifestation of systemic disease. Treatment includes chemotherapy and radiation, which may improve orbital disease; however, the overall prognosis remains poor.
Topics: Humans; Male; Aged; Middle Aged; Female; Retrospective Studies; Multiple Myeloma; Orbital Diseases; Exophthalmos; Oculomotor Muscles
PubMed: 36661857
DOI: 10.1097/IOP.0000000000002314 -
European Journal of Ophthalmology Sep 2023Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal... (Review)
Review
Plasma cell dyscrasias are a wide range of severe monoclonal gammopathies caused by pre-malignant or malignant plasma cells that over-secrete an abnormal monoclonal antibody. These disorders are associated with various systemic findings, including ophthalmological disorders. A search of PubMed, EMBASE, Scopus and Cochrane databases was performed in March 2021 to examine evidence pertaining to ocular complications in patients diagnosed with plasma cell dyscrasias. This review outlines the ocular complications associated with smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, plasmacytomas, multiple myeloma, Waldenström's macroglobulinemia, systemic amyloidosis, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes (POEMS) syndrome, and cryoglobulinemia. Although, the pathological mechanisms are not completely elucidated yet, wide-ranging ocular presentations have been identified over the years, evolving both the anterior and posterior segments of the eye. Moreover, the presenting symptoms also help in early diagnosis in asymptomatic patients. Therefore, it is imperative for the treating ophthalmologist and oncologist to maintain a high clinical suspicion for identifying the ophthalmological signs and diagnosing the underlying disease, preventing its progression through efficacious treatment strategies.
Topics: Humans; Paraproteinemias; Eye; Eye Diseases; Treatment Outcome
PubMed: 36760117
DOI: 10.1177/11206721231155974 -
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 -
Hematology/oncology Clinics of North... Aug 2023Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia (WM), which is caused by infiltration of the malignant lymphoplasmacytic cells in the... (Review)
Review
Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia (WM), which is caused by infiltration of the malignant lymphoplasmacytic cells in the central nervous system. Patients can present with a diverse range of neurologic symptoms, and differentiation with other comorbidities seen in WM, such as immunoglobulin M-related polyneuropathy, can be challenging. Both the rarity of this disorder and the heterogeneity of the clinical presentation often cause a significant diagnostic delay with the risk of permanent neurologic damage. This review summarizes current knowledge regarding diagnosis, treatment and prognosis of Bing-Neel syndrome.
Topics: Humans; Waldenstrom Macroglobulinemia; Delayed Diagnosis; Prognosis; Central Nervous System
PubMed: 37258354
DOI: 10.1016/j.hoc.2023.04.008