Emerging agents and regimens for multiple myeloma

Yang, Yang; Li, Yang; Gu, Huiyao; Dong, Mengmeng; Zhang, Cai

doi:10.1186/s13045-020-00980-5

Cited by 63 publications

(68 citation statements)

References 141 publications

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“…The median overall survival of MM patients has been improved to 5 years because of the introduction of new drugs [ 99 ]. Although the survival of patients is increasing with the continuous progress of therapeutic regimens, MM is still an incurable disease and almost all MM patients eventually relapsed [ 100 ]. Many bispecific T cell-recruiting antibodies for the treatment of MM have been developed rapidly in recent years.…”

Section: Mechanisms Of Bite Actionmentioning

confidence: 99%

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

et al. 2021

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Harnessing the power of immune cells, especially T cells, to enhance anti-tumor activities has become a promising strategy in clinical management of hematologic malignancies. The emerging bispecific antibodies (BsAbs), which recruit T cells to tumor cells, exemplified by bispecific T cell engagers (BiTEs), have facilitated the development of tumor immunotherapy. Here we discussed the advances and challenges in BiTE therapy developed for the treatment of hematologic malignancies. Blinatumomab, the first BiTE approved for the treatment of acute lymphocytic leukemia (ALL), is appreciated for its high efficacy and safety. Recent studies have focused on improving the efficacy of BiTEs by optimizing treatment regimens and refining the molecular structures of BiTEs. A considerable number of bispecific T cell-recruiting antibodies which are potentially effective in hematologic malignancies have been derived from BiTEs. The elucidation of mechanisms of BiTE action and neonatal techniques used for the construction of BsAbs can improve the treatment of hematological malignancies. This review summarized the features of bispecific T cell-recruiting antibodies for the treatment of hematologic malignancies with special focus on preclinical experiments and clinical studies.

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Section: Mechanisms Of Bite Actionmentioning

confidence: 99%

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

et al. 2021

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“…2 School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, China. 3 Shanghai Unicar-Therapy Bio-Medicine Technology Co., Ltd, Shanghai, China. 4 Department of Hematology, The Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…Multiple myeloma (MM) is still an incurable hematological malignancy, as most of MM patients eventually relapse or become refractory [ 1 , 2 ]. Strikingly, the CAR-T cell therapy has achieved satisfactory efficacy in patients with relapsed or refractory MM in recent years [ 3 ]. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics [ 4 ].…”

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confidence: 99%

CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients

Kang²,

Yang

et al. 2021

J Hematol Oncol

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The chimera antigen receptor (CAR) T cell therapy is a novel and potential targeted therapy and has achieved satisfactory efficacy in patients with relapsed or refractory multiple myeloma (MM) in recent years. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics. To explore the potential biomarkers in plasma for evaluating CRS and clinical efficacy, we performed metabolomic and lipidomic profiling of plasma samples from 17 relapsed or refractory MM patients received CAR-T therapy. Our study showed that glycerophosphocholine (GPC), an intermediate of platelet-activating factor (PAF)-like molecule, was significantly decreased when the participants underwent CRS, and the remarkable elevation of lysophosphatidylcholines (lysoPCs), which were catalyzed by lysoPC acyltransferase (LPCAT) was a distinct metabolism signature of relapsed or refractory MM patients with prognostic value post-CAR-T therapy. Both GPC and lysoPC are involved in platelet-activating factor (PAF) remodeling pathway. Besides, these findings were validated by LPCAT1 expression, a key factor in the PAF pathway, associated with poor outcome in three MM GEP datasets of MM. In conclusion, CAR-T therapy alters PAF synthesis in MM patients, and targeting PAF remodeling may be a promising strategy to enhance MM CAR-T therapy.

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“…Daratumumab (Dara), the first FDA-approved CD38 mAb, has clearly demonstrated its therapeutic benefit, and set the new standard for future myeloma drug approval (failed IMIDs, proteosome inhibitors and CD38 mAb) [ 46 ]. Dara in combination with lenalidomide and dexamethasone (Rd) (MAIA trial), or with bortezomib, melphalan, prednisone (VMP) (ALCYONE trial), was recently approved by the FDA as the frontline therapy for transplant ineligible NDMM [ 47 , 48 ].…”

Section: Introductionmentioning

confidence: 99%

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

Hou

et al. 2021

J Hematol Oncol

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Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.

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Emerging agents and regimens for multiple myeloma

Cited by 63 publications

References 141 publications

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies

CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients

Novel agents and regimens for hematological malignancies: recent updates from 2020 ASH annual meeting

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