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BMC Cancer Nov 2023Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM.
METHODS
PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched. We included studies investigating the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Overall response rates (ORR), stringent complete response rates (sCR), complete response rates (CR), very good partial response rates (VGPR), partial response rates (PR), stable disease (SD), progressive disease (PD) and adverse events were synthesized using either a random-effects model or a fixed-effects model.
RESULTS
A total of 7 clinical trials with 482 patients with RRMM were included. Concerning venetoclax with other agents, the pooled ORR, sCR, CR, VGPR, PR, SD, and PD were 0.76 (95% CIs: 0.62, 0.87), 0.11 (95% CIs: 0.04, 0.21), 0.18 (95% CIs: 0.11, 0.26), 0.16 (95% CIs: 0.12, 0.25), 0.29 (95% CIs: 0.25, 0.34), 0.07 (95% CIs: 0.05, 0.10), and 0.11 (95% CIs: 0.04, 0.23). The overall rate of adverse events ≥ Grade 3 was 0.84 (95% CIs: 0.77, 0.91). The most common non-hematologic adverse events were nausea, diarrhea, fatigue, back pain, and vomiting; hematologic adverse events included thrombocytopenia, neutropenia, anemia, leukopenia, and lymphopenia.
CONCLUSIONS
This study indicates that venetoclax alone or in combination with other agents reveals favorable treatment responses and acceptable adverse events in treating RRMM.
Topics: Humans; Multiple Myeloma; Treatment Outcome; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Dexamethasone
PubMed: 37924016
DOI: 10.1186/s12885-023-11553-3 -
Clinics in Laboratory Medicine Sep 2023Flow cytometry plays a critical role in the diagnosis, prognostication, therapy response evaluation, and clinical management of plasma cell neoplasms. The review... (Review)
Review
Flow cytometry plays a critical role in the diagnosis, prognostication, therapy response evaluation, and clinical management of plasma cell neoplasms. The review summarizes how flow cytometry is used in the initial evaluation to distinguish primary and secondary clonal plasma cell populations from each other and from reactive plasma cells. We further illustrate the kinds of prognostic information the assessment can provide at diagnosis and disease follow-up of primary plasma cell neoplasms. Technical requirements for MRD assays and their use in therapy efficacy assessment and clinical decision-making in multi-myeloma are discussed.
Topics: Humans; Multiple Myeloma; Flow Cytometry; Neoplasms, Plasma Cell; Clinical Decision-Making
PubMed: 37481317
DOI: 10.1016/j.cll.2023.05.003 -
International Journal of Molecular... Nov 2023Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several... (Review)
Review
Multiple myeloma (MM) is a hematological malignancy originated in the bone marrow and characterized by unhindered plasma cell proliferation that results in several clinical manifestations. Although the main role of blood platelets lies in hemostasis and thrombosis, platelets also play a pivotal role in a number of other pathological conditions. Platelets are the less-explored components from the tumor microenvironment in MM. Although some studies have recently revealed that MM cells have the ability to activate platelets even in the premalignant stage, this phenomenon has not been widely investigated in MM. Moreover, thrombocytopenia, along with bleeding, is commonly observed in those patients. In this review, we discuss the hemostatic disturbances observed in MM patients and the dynamic interaction between platelets and myeloma cells, along with present and future potential avenues for the use of platelets for diagnostic and therapeutic purposes.
Topics: Humans; Blood Platelets; Multiple Myeloma; Hemorrhage; Hemostasis; Thrombosis; Cell Communication; Drug Delivery Systems; Tumor Microenvironment
PubMed: 37958838
DOI: 10.3390/ijms242115855 -
Hematology. American Society of... Dec 2023Multiple myeloma is a clinically and biologically highly heterogeneous disease, as the overall survival can vary from more than a decade in patients with standard risk... (Review)
Review
Multiple myeloma is a clinically and biologically highly heterogeneous disease, as the overall survival can vary from more than a decade in patients with standard risk disease treated with intensive chemotherapy to 2-3 years in patients with high-risk features. The current staging systems, which rely on baseline biological risk factors to stratify patients into groups with differing risks of progression or death, are sometimes suboptimal tools for identifying high-risk patients. This is particularly evident when considering the so-called functional high-risk patients-patients who do not necessarily display baseline high-risk features but typically show a suboptimal response to induction therapy or relapse early after treatment initiation: the survival of these patients is particularly poor even in the context of newer therapies. The prompt identification, as well as a consistent definition, of this subset of patients, as well as their management, currently represents an unmet medical need. In this review we explore the main characteristics of functional high-risk patients, the available known risk factors and scoring systems, and the possible management.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local
PubMed: 38066896
DOI: 10.1182/hematology.2023000443 -
Pathology, Research and Practice Aug 2023Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with... (Review)
Review
Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.
Topics: Humans; MicroRNAs; Multiple Myeloma; Phosphatidylinositol 3-Kinases; Drug Resistance, Neoplasm; Prognosis; Gene Expression Regulation, Neoplastic
PubMed: 37499518
DOI: 10.1016/j.prp.2023.154704 -
Blood Advances Dec 2023
Topics: Humans; Multiple Myeloma; Bortezomib; Thalidomide; Renal Insufficiency; Dexamethasone
PubMed: 37922425
DOI: 10.1182/bloodadvances.2023011428 -
The Journal of Neuroscience : the... Jul 2023Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly...
Multiple myeloma (MM) is a neoplasia of B plasma cells that often induces bone pain. However, the mechanisms underlying myeloma-induced bone pain (MIBP) are mostly unknown. Using a syngeneic MM mouse model, we show that periosteal nerve sprouting of calcitonin gene-related peptide (CGRP) and growth associated protein 43 (GAP43) fibers occurs concurrent to the onset of nociception and its blockade provides transient pain relief. MM patient samples also showed increased periosteal innervation. Mechanistically, we investigated MM induced gene expression changes in the dorsal root ganglia (DRG) innervating the MM-bearing bone of male mice and found alterations in pathways associated with cell cycle, immune response and neuronal signaling. The MM transcriptional signature was consistent with metastatic MM infiltration to the DRG, a never-before described feature of the disease that we further demonstrated histologically. In the DRG, MM cells caused loss of vascularization and neuronal injury, which may contribute to late-stage MIBP. Interestingly, the transcriptional signature of a MM patient was consistent with MM cell infiltration to the DRG. Overall, our results suggest that MM induces a plethora of peripheral nervous system alterations that may contribute to the failure of current analgesics and suggest neuroprotective drugs as appropriate strategies to treat early onset MIBP. Multiple myeloma (MM) is a painful bone marrow cancer that significantly impairs the quality of life of the patients. Analgesic therapies for myeloma-induced bone pain (MIBP) are limited and often ineffective, and the mechanisms of MIBP remain unknown. In this manuscript, we describe cancer-induced periosteal nerve sprouting in a mouse model of MIBP, where we also encounter metastasis to the dorsal root ganglia (DRG), a never-before described feature of the disease. Concomitant to myeloma infiltration, the lumbar DRGs presented blood vessel damage and transcriptional alterations, which may mediate MIBP. Explorative studies on human tissue support our preclinical findings. Understanding the mechanisms of MIBP is crucial to develop targeted analgesic with better efficacy and fewer side effects for this patient population.
Topics: Humans; Mice; Male; Animals; Multiple Myeloma; Quality of Life; Pain; Bone Diseases; Nerve Tissue; Ganglia, Spinal
PubMed: 37286351
DOI: 10.1523/JNEUROSCI.0404-23.2023 -
European Journal of Haematology Jan 2024The introduction of chimeric antigen receptor (CAR) T cells revolutionized treatment of relapsed and refractory multiple myeloma (RRMM) in recent years. Currently, two... (Review)
Review
The introduction of chimeric antigen receptor (CAR) T cells revolutionized treatment of relapsed and refractory multiple myeloma (RRMM) in recent years. Currently, two CAR T cell products-idecabtagene vicleucel and ciltacabtagene autoleucel-are approved in the United States and the European Union to treat patients with three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody. Moreover, seminal phase III trials of both agents in earlier lines of therapy have been published recently. Despite unprecedented rates of deep and lasting remissions in RRMM, there are still areas of uncertainty regarding the optimal use and distribution of CAR T cells in multiple myeloma. In the current review, we discuss the available data on approved CAR T cell products as well as unmet clinical needs and ongoing developments to optimize usage of this promising treatment modality in multiple myeloma.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Antiviral Agents; Molecular Targeted Therapy; Proteasome Inhibitors
PubMed: 37547971
DOI: 10.1111/ejh.14051 -
Hematology/oncology Clinics of North... Apr 2024Multiple myeloma is characterized by a highly heterogeneous disease distribution within the bone marrow-containing skeletal system. In this review, we introduce the... (Review)
Review
Multiple myeloma is characterized by a highly heterogeneous disease distribution within the bone marrow-containing skeletal system. In this review, we introduce the molecular mechanisms underlying clonal heterogeneity and the spatio-temporal evolution of myeloma. We discuss the clinical impact of clonal heterogeneity, which is thought to be one of the biggest obstacles to overcome therapy resistance and to achieve cure.
Topics: Humans; Multiple Myeloma; Bone Marrow; Clonal Evolution
PubMed: 38195308
DOI: 10.1016/j.hoc.2023.12.012 -
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