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Annals of Hematology Jun 2024Improvement in the therapeutics for multiple myeloma (MM) has been continuously developed owing to the application of novel drugs and technologies in the last 20 years.... (Review)
Review
Improvement in the therapeutics for multiple myeloma (MM) has been continuously developed owing to the application of novel drugs and technologies in the last 20 years. The standard first-line therapy for MM consists of a three-drug induction regimen based on immunomodulatory drugs and proteasome inhibitors combined with autologous stem cell transplantation. However, MM remains incurable; therefore, therapies for relapsed/refractory MM (RRMM) are emerging and evolving rapidly. This study aimed to summarize and review the results of RRMM trials over the past 5 years to provide a holistic overview and insights for practitioners in related fields and to provide additional ideas for clinical trialists. This study shows that daratumumab and isatuximab continue to significantly advance as treatment options. Additionally, novel antibody drugs, such as elotuzumab and selinexor, as well as bispecific antibodies, teclistamab and talquetamab, are currently undergoing clinical research with promising outcomes. However, chimeric antigen receptor-T cell therapy targeting B-cell maturation antigen remains the optimal approach for MM treatment.
Topics: Multiple Myeloma; Humans; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunotherapy, Adoptive; Recurrence; Antineoplastic Combined Chemotherapy Protocols; Transplantation, Autologous; Clinical Trials as Topic; Antibodies, Bispecific; Hematopoietic Stem Cell Transplantation
PubMed: 38609727
DOI: 10.1007/s00277-024-05730-y -
Journal of Hematology & Oncology Jul 2023Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in...
Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Dexamethasone; Europe; Lenalidomide; Multiple Myeloma
PubMed: 37468911
DOI: 10.1186/s13045-023-01474-w -
Nature Reviews. Disease Primers Jun 2024Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin... (Review)
Review
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage. Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option. If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
Topics: Multiple Myeloma; Humans; Dexamethasone; Lenalidomide; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Melphalan; Thalidomide; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38937492
DOI: 10.1038/s41572-024-00529-7 -
Journal of Cancer Research and Clinical... Aug 2023Multiple myeloma (MM) is the second most common hematological cancer that has no cure. Although currently there are several novel drugs, most MM patients experience drug... (Review)
Review
Multiple myeloma (MM) is the second most common hematological cancer that has no cure. Although currently there are several novel drugs, most MM patients experience drug resistance and disease relapse. The results of previous studies suggest that aberrant mitochondrial function may contribute to tumor progression and drug resistance. Mitochondrial DNA mutations and metabolic reprogramming have been reported in MM patients. Several preclinical and clinical studies have shown encouraging results of mitochondria-targeting therapy in MM patients. In this review, we have summarized our current understanding of mitochondrial biology in MM. More importantly, we have reviewed mitochondrial targeting strategies in MM treatment.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Mitochondria; Mutation
PubMed: 36928159
DOI: 10.1007/s00432-023-04672-8 -
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 -
Giornale Italiano Di Nefrologia :... Oct 2023Myeloma cast nephropathy is the most common cause of acute kidney injury in patients affected by multiple myeloma. The mainstay of management of cast nephropathy is the... (Review)
Review
Myeloma cast nephropathy is the most common cause of acute kidney injury in patients affected by multiple myeloma. The mainstay of management of cast nephropathy is the clone-based therapy by reducing production and thereby precipitation of light chains. Adjuvant therapy consists of inducing high urine volume flow and alkalinisation, where possible. Extracorporeal removal of light chains is still debated and the advantages of these procedures are not established. The use of safe and low expensive membranes may encourage their use and address their utility.
Topics: Humans; Immunoglobulin Light Chains; Renal Dialysis; Treatment Outcome; Multiple Myeloma; Acute Kidney Injury
PubMed: 38007838
DOI: No ID Found -
The Lancet. Oncology Aug 2023
Topics: Humans; Multiple Myeloma; Receptors, Chimeric Antigen; Point-of-Care Systems; T-Lymphocytes; Immunotherapy, Adoptive
PubMed: 37414061
DOI: 10.1016/S1470-2045(23)00269-3 -
Hematology/oncology Clinics of North... Apr 2024Measurable (minimal) residual disease (MRD) has already proven to be one of the most important prognostic factors in multiple myeloma (MM). Each improvement in the depth... (Review)
Review
Measurable (minimal) residual disease (MRD) has already proven to be one of the most important prognostic factors in multiple myeloma (MM). Each improvement in the depth of MRD testing has led to superior discrimination of outcomes, and sustained MRD negativity seems to be paramount to durable responses. Peripheral blood assays to assess for MRD are still under investigation but hold promise as complementary tools to bone marrow MRD assays such as next-generation sequencing and flow cytometry. Herein, the authors explore the evidence and potential benefits and drawbacks of MRD-adapted clinical decision-making in MM.
Topics: Humans; Multiple Myeloma; Bone Marrow; Neoplasm, Residual; Flow Cytometry; High-Throughput Nucleotide Sequencing
PubMed: 38184470
DOI: 10.1016/j.hoc.2023.12.009 -
International Immunopharmacology Jun 2024Multiple myeloma (MM), a malignancy of plasma cells, is an incurable disease that is characterized by the neoplastic proliferation of plasma cells leading to extensive... (Review)
Review
Multiple myeloma (MM), a malignancy of plasma cells, is an incurable disease that is characterized by the neoplastic proliferation of plasma cells leading to extensive skeletal destruction. This includes osteolytic lesions, osteopenia, and pathologic fractures. MM is clinically manifested through bone pain, renal insufficiency, hypercalcemia, anemia, and recurrent infections. Its prevalence and the need for effective treatment underscore the importance of this research. Recent advancements in MM therapy have been significant, particularly with the integration of daratumumab into first-line treatments. The use of daratumumab in regimens such as DRD (Daratumumab, Revlimid, Dexamethasone) and D-RVd (Daratumumab, Lenalidomide, Bortezomib, Dexamethasone) represents a paradigm shift in the treatment landscape. GRIFFIN and CASSIOPEIA trials have highlighted the efficacy of these regimens, particularly in prolonging progression-free survival and deepening patient responses. The shift from older regimens like MPV (Melphalan, Prednisone, Velcade) to more effective ones like DRD and RVD has been pivotal in treatment strategies. This review also focuses on the potential of Chimeric Antigen Receptor T-cell therapy and bispecific antibodies in MM. CAR-T therapy, which has shown success in other hematological malignancies, is being explored for its ability to specifically target MM cells. The latest clinical trials and research findings are analyzed to evaluate the efficacy and challenges of CAR-T therapy in MM. Additionally, the role of bispecific antibodies, which are designed to bind both cancer cells and T cells, is explored. These antibodies offer a unique mechanism that could complement the effects of CAR-T therapy.
Topics: Humans; Multiple Myeloma; Antibodies, Bispecific; Immunotherapy, Adoptive; Animals; Receptors, Chimeric Antigen
PubMed: 38733817
DOI: 10.1016/j.intimp.2024.112043 -
Haematologica May 2024
Topics: Humans; Multiple Myeloma
PubMed: 37981890
DOI: 10.3324/haematol.2023.284292