Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma, acute myeloid leukemia, and Hodgkin lymphoma (HL). At the same time, the design and production of chimeric antigen receptor T cells are being advanced so that this therapy can be more widely utilized. Cytokine release syndrome and neurotoxicity are common, but they are treatable and fully reversible. This review will review available data as well as future developments and challenges in the field.
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PMID:The Promise of Chimeric Antigen Receptor Engineered T Cells in the Treatment of Hematologic Malignancies. 2684 Oct 14

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.
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PMID:Management of cytokine release syndrome related to CAR-T cell therapy. 3157 Nov 60

Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.
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PMID:CAR T-cell therapy: is it prime time in myeloma? 3171 64

Chimeric antigen receptor (CAR)-modified T cell therapy is increasingly administered for hematological malignancies. Cytokine release syndrome (CRS) is a common and severe complication of CAR-T therapy. In the present case, a 62-year-old male patient was diagnosed with relapsed and refractory multiple myeloma (RRMM). Treated with CART-CD19/BCMA therapy, his symptoms remitted, during which occasional but severe CRS associated with coagulation disorder still appeared, as evidenced by the coexistence of a huge thrombosis and bleeding tendency. Through the First Generation Sequencing, we extracted genomic DNA from the patient's peripheral blood to analyze the distribution of polymorphism at the -572C/G site of the promoter of IL-6 gene. The results showed that the genotype of -572C/G promoter polymorphism was CC, indicating that high level of IL-6 and -572C/G polymorphism might be associated with the risk of thrombotic disorders. We concluded that immediate diagnosis and appropriate treatment of coagulopathy could reduce CRS-related mortality.
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PMID:Coexistence Of A Huge Venous Thromboembolism And Bleeding Tendency In Cytokine Release Syndrome During CAR-T Therapy. 3180 5

Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma.
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PMID:CAR T-cell therapy: is it prime time in myeloma? 3180 95

B-cell maturation antigen (BCMA)-targeting bispecific antibodies and bispecific T-cell engagers (BiTEs) redirect T-cells to BCMA-expressing multiple myeloma (MM) cells. These MM cells are subsequently eliminated via various mechanisms of action including the release of granzymes and perforins. Several phase 1, dose-escalation studies show pronounced activity of BCMA-targeting bispecific antibodies, including teclistamab, AMG420 and CC-93269, in heavily pretreated MM patients. Cytokine release syndrome is the most common adverse event, which can be adequately managed with tocilizumab or steroids. Several clinical trials are currently evaluating combination therapy with a BCMA-specific bispecific antibody, based on preclinical findings showing that immunomodulatory drugs or CD38-targeting antibodies enhance the activity of bispecific antibodies. In addition, bispecific antibodies, targeting other MM cell surface antigens (i. e. GPRC5D, CD38 and FcRH5), are also evaluated in early phase clinical trials. Such bispecific antibodies, targeting other antigens, may be given to patients with low baseline BCMA expression, disease with substantial heterogeneity in BCMA expression, following prior BCMA-targeted therapy, or combined with BCMA bispecific antibodies to prevent development of antigen escape.
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PMID:T-cell redirecting bispecific antibodies targeting BCMA for the treatment of multiple myeloma. 3322 97