BCMA-targeted immunotherapy for multiple myeloma

Published on Sep 17, 2020in Journal of Hematology & Oncology17.388
· DOI :10.1186/S13045-020-00962-7
Bo Yu2
Estimated H-index: 2
 (Lincoln Hospital), Tianbo Jiang1
Estimated H-index: 1
 (NYMC: New York Medical College), Delong Liu54
Estimated H-index: 54
 (NYMC: New York Medical College)
Sources
Abstract
B cell maturation antigen (BCMA) is a novel treatment target for multiple myeloma (MM) due to its highly selective expression in malignant plasma cells (PCs). Multiple BCMA-targeted therapeutics, including antibody-drug conjugates (ADC), chimeric antigen receptor (CAR)-T cells, and bispecific T cell engagers (BiTE), have achieved remarkable clinical response in patients with relapsed and refractory MM. Belantamab mafodotin-blmf (GSK2857916), a BCMA-targeted ADC, has just been approved for highly refractory MM. In this article, we summarized the molecular and physiological properties of BCMA as well as BCMA-targeted immunotherapeutic agents in different stages of clinical development.
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May 27, 2020·Biomarker research6.15
#1Yuru Nie (Southern Medical University)H-Index: 1
#2Weiqing Lu (Southern Medical University)H-Index: 1
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Chimeric antigen receptor (CAR) T cell therapy, especially anti-CD19 CAR T cell therapy, has shown remarkable anticancer activity in patients with relapsed/refractory acute lymphoblastic leukemia, demonstrating an inspiring complete remission rate. However, with extension of the follow-up period, the limitations of this therapy have gradually emerged. Patients are at a high risk of early relapse after achieving complete remission. Although there are many studies with a primary focus on the mecha...
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8505Background: JNJ-68284528 (JNJ-4528) is a chimeric antigen receptor T (CAR-T) cell therapy containing 2 BCMA-targeting single-domain antibodies. Here we present updated CARTITUDE-1 (NCT03548207)...
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May 25, 2020·Journal of Clinical Oncology44.54
#1Nikhil C. Munshi (Harvard University)H-Index: 151
#2Larry D. Anderson (UTSW: University of Texas Southwestern Medical Center)H-Index: 16
Last. Jesús F. San Miguel (University of Navarra)H-Index: 113
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8503Background: Outcomes are poor in triple-class exposed RRMM patients (pts) who progress on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies (mAbs). Ide-cel, a BC...
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Feb 1, 2020·Lancet Oncology41.32
#7Al-Ola Abdallah (KU: University of Kansas)H-Index: 9
Summary Background Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study. Methods DREAMM-2 is an open-label, two-arm, phase 2 study done at 58 multiple myeloma specialty centres in eight countries. Patients (aged ≥18 years) with rel...
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Dec 10, 2019·Journal of Hematology & Oncology17.39
#1Jiangmei Liu (CCDC: Chinese Center for Disease Control and Prevention)H-Index: 24
#2Weiping Liu (PKU: Peking University)H-Index: 12
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The accurate information about burden of multiple myeloma (MM) at national and provincial level remains unknown in China. Following the general analytical strategy used in GBD 2016, the age-, sex-, and province-specific incidence and mortality in China were analyzed. Trends in the incidence and mortality from 2006 to 2016 were evaluated. It was estimated that there were 16,500 new cases and 10,300 deaths of multiple myeloma in China in 2016. The age-standardized incidence rates (ASIR) and mortal...
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Nov 29, 2019·Journal of Hematology & Oncology17.39
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The approval of two chimeric antigen receptor-modified T cell types by the US Food and Drug Administration (FDA) for the treatment of hematologic malignancies is a milestone in immunotherapy; however, the application of CAR-T cells has been limited by antigen escape and on-target, off-tumor toxicities. Therefore, it may be a potentially effective strategy to select appropriate targets and to combine multi-antigen-targeted CAR-T cells with “OR”, “AND” and “NOT” Boolean logic gates. We summarize t...
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Nov 21, 2019·Journal of Hematology & Oncology17.39
#1Chao Wu (Nanjing Medical University)H-Index: 4
#2Lina Zhang (Nanjing Medical University)H-Index: 1
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Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite the advent of numerous new drugs such as proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. Furthermore, the toxicities of CAR-T ce...
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Nov 15, 2019·Biomarker research6.15
#1Delong Liu (Zhengzhou University)H-Index: 54
Tumor-associated antigens (TAA) or cancer biomarkers are major targets for cancer therapies. Antibody- based agents targeting the cancer biomarkers include monoclonal antibodies (MoAbs), radiolabeled MoAbs, bispecific T cell engagers, and antibody-drug conjugates. Antibodies targeting CD19, CD20, CD22, CD30, CD33, CD38, CD79B and SLAMF7 are in clinical applications for hematological malignancies. CD123, CLL-1, B cell maturation antigen, and CD138 are targets for cancer immunotherapeutic agents, ...
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Nov 13, 2019·Blood23.63
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Nov 13, 2019·Blood23.63
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Sep 23, 2021·Journal of Hematology & Oncology17.39
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New approaches to stratify multiple myeloma patients based on prognosis and therapeutic decision-making, or prediction, are needed since patients are currently managed in a similar manner regardless of individual risk factors or disease characteristics. However, despite new and improved biomarkers for determining the prognosis of patients, there is currently insufficient information to utilise biomarkers to intensify, reduce or altogether change treatment, nor to target patient-specific biology ...
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Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody–drug c...
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Aug 21, 2021·Journal of Hematology & Oncology17.39
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Cell therapy has evolved rapidly in the past several years with more than 250 clinical trials ongoing around the world. While more indications of cellular therapy with chimeric antigen receptor – engineered T cells (CAR-T) are approved for hematologic malignancies, new concepts and strategies of cellular therapy for solid tumors are emerging and are discussed. These developments include better selections of targets by shifting from tumor-associated antigens to personalized tumor-specific neoanti...
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Jul 23, 2021·Journal of Hematology & Oncology17.39
#1Christopher T. Su (UM: University of Michigan)H-Index: 5
#2J Christine Ye (UM: University of Michigan)H-Index: 2
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Jan 1, 2021·Frontiers in Oncology6.24
#4Jonathan Carmichael (Leeds Teaching Hospitals NHS Trust)
Background The treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world. Methods This was a retrospective cohort review of pat...
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Multiple myeloma is a plasma cell malignancy that primarily affects the elderly. The global burden of multiple myeloma is increasing in many countries due to an aging population. Despite recent advances in therapy, myeloma remains an incurable disease, highlighting the pressing need for new therapies. Accumulating evidence supports that triggering the host immune system is a critical therapeutic mechanism of action by various anti-myeloma therapies. These anti-myeloma therapies include proteasom...
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Biologically-based therapies increasingly rely on the endocytic cycle of internalization and exocytosis of target receptors for cancer therapies. However, receptor trafficking pathways (endosomal sorting (recycling, lysosome localization) and lateral membrane movement) are often dysfunctional in cancer. Antibody-drug conjugates (ADCs) have revitalized the concept of targeted chemotherapy by coupling inhibitory antibodies to cytotoxic payloads. Significant advances in ADC technology and format, a...
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