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Home Healthcare NowMultiple myeloma (MM) is a cancer that arises from plasma cells in bone marrow. Approximately 35,730 Americans received a new diagnosis and MM will claim the lives of an... (Review)
Review
Multiple myeloma (MM) is a cancer that arises from plasma cells in bone marrow. Approximately 35,730 Americans received a new diagnosis and MM will claim the lives of an estimated 12,590 people in 2023. Complications of the disease process include anemia, leukopenia, thrombocytopenia, renal failure, severe pain, bone loss, and hypercalcemia. Patients with MM have a high risk for pathological fractures. For most forms of MM there are effective treatments that may result in long-term remission using multi-drug regimens. Although the medications approved in the United States to treat MM generally produce good outcomes, they have serious, and potentially life-threatening adverse effects. In addition, patients with specific genetic variations are at high risk for relapse. Communication with the oncology team and early intervention in the event of adverse effects of medications, complications of the disease process, or evidence of relapse are important to obtain the best possible outcome. Patients are easily overwhelmed with a three- to four-drug treatment regimen with some drugs given intravenously and/or subcutaneously at the clinic, and others taken orally at home on specific days of each 28-day cycle. Home care nursing is needed to assess for tolerance, adverse effects, and to address patient concerns. Medication management and teaching are very important in guiding patients to safely manage a schedule that changes daily. In addition, the high risk of pathological fractures and serious injury if the patient should fall supports the need for physical and occupational therapy fall prevention and safety education and exercise programs to help avert decline in functional status and combat cancer-related fatigue.
Topics: Humans; Multiple Myeloma; Antineoplastic Agents
PubMed: 38709580
DOI: 10.1097/NHH.0000000000001249 -
Giornale Italiano Di Nefrologia :... Oct 2023Immunoglobulin Light Chain Amyloidosis (AL) is a progressive disease which leads to organ dysfunction and death. Tremendous progress has been made in staging, response,... (Review)
Review
Immunoglobulin Light Chain Amyloidosis (AL) is a progressive disease which leads to organ dysfunction and death. Tremendous progress has been made in staging, response, and treatment. The key to better survival though is early diagnosis which can be difficult since the symptoms are often nonspecific and can be seen in more common conditions. Once the diagnosis is confirmed, staging systems are available to provide prognosis on overall and renal survival. There are a number of treatments now available that are effective and well-tolerated. Response criteria have also been developed for hematologic and renal response in order to maximize response and minimize adverse effects. Newer therapies are being developed in particular anti-fibril therapies that are in clinical trials. For those patients who had a very good partial response or better, kidney transplantation may be an option if the kidney failure is not reversed.
Topics: Humans; Immunoglobulin Light Chains; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Kidney; Kidney Transplantation
PubMed: 38007836
DOI: No ID Found -
Nature Cancer Dec 2023Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody,...
Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody, progress prematurely. By integrating tumor whole-genome and microenvironment single-cell RNA sequencing from upfront phase 2 trials using carfilzomib, lenalidomide and dexamethasone with daratumumab ( NCT03290950 ), we show how distinct genomic drivers including high APOBEC mutational activity, IKZF3 and RPL5 deletions and 8q gain affect clinical outcomes. Furthermore, evaluation of paired bone marrow profiles, taken before and after eight cycles of carfilzomib, lenalidomide and dexamethasone with daratumumab, shows that numbers of natural killer cells before treatment, high T cell receptor diversity before treatment, the disappearance of sustained immune activation (that is, B cells and T cells) and monocyte expansion over time are all predictive of sustained minimal residual disease negativity. Overall, this study provides strong evidence of a complex interplay between tumor cells and the immune microenvironment that is predictive of clinical outcome and depth of treatment response in patients with newly diagnosed multiple myeloma treated with highly effective combinations containing anti-CD38 antibodies.
Topics: Humans; Dexamethasone; Genomics; Immunotherapy; Lenalidomide; Multiple Myeloma; Tumor Microenvironment
PubMed: 37945755
DOI: 10.1038/s43018-023-00657-1 -
Current Neurology and Neuroscience... Nov 2023Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset, acquired, muscle disease that can be associated with monoclonal gammopathy or HIV infection. The... (Review)
Review
PURPOSE OF REVIEW
Sporadic late-onset nemaline myopathy (SLONM) is a rare adult-onset, acquired, muscle disease that can be associated with monoclonal gammopathy or HIV infection. The pathological hallmark of SLONM is the accumulation of nemaline rods in muscle fibers. We review here current knowledge about its presentation, pathophysiology, and management.
RECENT FINDINGS
SLONM usually manifests with subacutely progressive proximal and axial weakness, but it can also present with chronic progressive weakness mimicking muscular dystrophy. The pathophysiology of the disease remains poorly understood, with evidence pointing to both autoimmune mechanisms and hematological neoplasia. Recent studies have identified histological, proteomic, and transcriptomic alterations that shed light on disease mechanisms and distinguish SLONM from inherited nemaline myopathies. A majority of SLONM patients respond to intravenous immunoglobulins, chemotherapy, or hematopoietic stem cell transplant. SLONM is a treatable myopathy, although its underlying etiology and pathomechanisms remain unclear. A high degree of suspicion should be maintained for this disease to reduce diagnostic delay and treatment in SLONM and facilitate its distinction from inherited nemaline myopathies.
Topics: Adult; Humans; Myopathies, Nemaline; HIV Infections; Delayed Diagnosis; Proteomics; Monoclonal Gammopathy of Undetermined Significance; Muscle, Skeletal
PubMed: 37856049
DOI: 10.1007/s11910-023-01311-0 -
Journal of Clinical Oncology : Official... Apr 2024Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years.
PURPOSE
Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years.
METHODS
To decipher and predict the molecular and clinical heterogeneity of NDMM, we assembled a series of 1,933 patients with available clinical, genomic, and therapeutic data.
RESULTS
Leveraging a comprehensive catalog of genomic drivers, we identified 12 groups, expanding on previous gene expression-based molecular classifications. To build a model predicting individualized risk in NDMM (IRMMa), we integrated clinical, genomic, and treatment variables. To correct for time-dependent variables, including high-dose melphalan followed by autologous stem-cell transplantation (HDM-ASCT), and maintenance therapy, a multi-state model was designed. The IRMMa model accuracy was significantly higher than all comparator prognostic models, with a c-index for OS of 0.726, compared with International Staging System (ISS; 0.61), revised-ISS (0.572), and R2-ISS (0.625). Integral to model accuracy was 20 genomic features, including 1q21 gain/amp, del 1p, loss, translocations, APOBEC mutational signatures, and copy-number signatures (reflecting the complex structural variant chromothripsis). IRMMa accuracy and superiority compared with other prognostic models were validated on 256 patients enrolled in the GMMG-HD6 (ClinicalTrials.gov identifier: NCT02495922) clinical trial. Individualized patient risks were significantly affected across the 12 genomic groups by different treatment strategies (ie, treatment variance), which was used to identify patients for whom HDM-ASCT is particularly effective versus patients for whom the impact is limited.
CONCLUSION
Integrating clinical, demographic, genomic, and therapeutic data, to our knowledge, we have developed the first individualized risk-prediction model enabling personally tailored therapeutic decisions for patients with NDMM.
Topics: Humans; Multiple Myeloma; Prognosis; Melphalan; Hematopoietic Stem Cell Transplantation; Genomics; Transplantation, Autologous; Retrospective Studies
PubMed: 38194610
DOI: 10.1200/JCO.23.01277 -
Brain and Nerve = Shinkei Kenkyu No... May 2024POEMS syndrome is a multisystem disorder associated with monoclonal plasma cell proliferation and the overproduction of vascular endothelial growth factors. The... (Review)
Review
POEMS syndrome is a multisystem disorder associated with monoclonal plasma cell proliferation and the overproduction of vascular endothelial growth factors. The prognosis of POEMS syndrome has significantly improved owing to anti-myeloma treatments such as thalidomide and autologous stem cell transplantation. Therefore, early diagnosis and appropriate treatment are becoming increasingly important. A thorough and comprehensive evaluation of both systemic symptoms and laboratory abnormalities associated with the disease is essential for early diagnosis. The collaboration between neurology and hematology is indispensable to ensure proper treatment.
Topics: POEMS Syndrome; Humans; Prognosis
PubMed: 38741495
DOI: 10.11477/mf.1416202642 -
Hematology/oncology Clinics of North... Apr 2024This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing... (Review)
Review
This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift toward myeloma involves ongoing immune impairment, affecting both innate and adaptive immunity. Intriguingly, even in advanced myeloma stages, susceptibility to immune effector cells persists. This insight highlights the intricate interplay between immune responses and the development of these conditions, paving the way for potential therapeutic interventions targeting immune modulation in the management of MGUS and myeloma.
Topics: Humans; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Disease Progression
PubMed: 38195307
DOI: 10.1016/j.hoc.2023.12.011 -
Expert Review of Anticancer Therapy May 2024The prognosis of multiple myeloma (MM) continues to improve. Recent progress in therapies, using immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and... (Review)
Review
INTRODUCTION
The prognosis of multiple myeloma (MM) continues to improve. Recent progress in therapies, using immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies, has greatly improved patients' outcomes. Despite these advancements, relapses still happen often, and patients can become resistant to the usual treatments. Newer treatments, such as chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA), have resulted in excellent outcomes in patients with limited treatment options. G protein - coupled receptor, class C group 5 member D (GPRC5D) is considered a very promising target with early results from clinical trials showing high response rates in patients with relapsed or refractory multiple myeloma.
AREAS COVERED
This review covers the efficacy and safety of CAR-T and BsAbs targeting GPRC5D in MM, focusing on talquetamab - the inaugural FDA-approved BsAb targeting GPRC5D. Talquetamab has exhibited promising response rates alongside a distinctive side effect profile. Additionally, ongoing trials examining talquetamab in combination with agents like daratumumab and teclistamab are discussed.
EXPERT OPINION
We offer insights into the potential utilization of various GPRC5D-based therapies in the treatment paradigm for MM, either independently or in combination with established therapies.
Topics: Humans; Multiple Myeloma; Receptors, G-Protein-Coupled; Immunotherapy, Adoptive; Molecular Targeted Therapy; Antibodies, Bispecific; Animals; Prognosis
PubMed: 38607646
DOI: 10.1080/14737140.2024.2343114 -
Medicina Clinica Sep 2023Monoclonal gammopathy of uncertain significance is a premalignant plasma cell neoplasm with a high prevalence in the population over 50 years of age and an annual risk... (Review)
Review
Monoclonal gammopathy of uncertain significance is a premalignant plasma cell neoplasm with a high prevalence in the population over 50 years of age and an annual risk of progression of 1%. Multiple recent studies have led to advances in understanding both the pathogenesis of these disorders and their risk of progression to other diseases. Patients require lifelong follow-up, and a multidisciplinary and risk-adapted approach is essential. In recent years, an increasing number of entities associated with a paraprotein, known as clinically significant monoclonal gammopathies, have been recognized.
Topics: Humans; Middle Aged; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma
PubMed: 37330390
DOI: 10.1016/j.medcli.2023.05.006 -
Blood Reviews Mar 2024Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC... (Review)
Review
Multiple myeloma is a plasma cell neoplasm driven by primary (e.g. hyperdiploidy; IGH translocations) and secondary (e.g. 1q21 gains/amplifications; del(17p); MYC translocations) chromosomal events. These are important to detect as they influence prognosis, therapeutic response and disease survival. Currently, cytogenetic testing is most commonly performed by interphase fluorescence in situ hybridisation (FISH) on aspirated bone marrow samples. A number of variations to FISH methodology are available, including prior plasma cell enrichment and incorporation of immunophenotypic plasma cell identification. Other molecular methods are increasingly being utilised to provide a genome-wide view at high resolution (e.g. single nucleotide polymorphism (SNP) microarray analysis) and these can detect abnormalities in most cases. Despite their wide application at diagnostic assessment, both FISH and SNP-array have relatively low sensitivity, limiting their use for identification of prognostically significant low-level sub-clones or for disease monitoring. Next-generation sequencing is increasingly being used to detect mutations and new FISH techniques such as by flow cytometry are in development and may address some of the current test limitations. Here we review the primary and secondary cytogenetic aberrations in myeloma and discuss the range of techniques available for their assessment.
Topics: Humans; Multiple Myeloma; Chromosome Aberrations; Translocation, Genetic; In Situ Hybridization, Fluorescence; Gene Rearrangement
PubMed: 38212176
DOI: 10.1016/j.blre.2024.101168