scholarly journals Effective anti-BCMA retreatment in multiple myeloma

2021 ◽  
Vol 5 (15) ◽  
pp. 3016-3020
Author(s):  
Nicolas Gazeau ◽  
David Beauvais ◽  
Ibrahim Yakoub-Agha ◽  
Suman Mitra ◽  
Timothy B. Campbell ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Great Promise ◽  
Central Question ◽  
Mechanisms Of Resistance ◽  
Car T Cells ◽  
Drug Conjugates ◽  
B Cell Maturation ◽  
Recent Emergence ◽  
Car T ◽  
Immunosuppressive Microenvironment

Abstract The recent emergence of anti–B-cell maturation antigen (BCMA) therapies holds great promise in multiple myeloma (MM). These include chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody-drug conjugates. Their development in clinical trials and further approval are changing the strategy for treating MM. Considering that a cure has not been reached, a central question in the coming years will be the possibility of using these therapies sequentially. Here, we report 2 cases of the serial use of anti-BCMA therapies with parallel monitoring of BCMA expression and anti-CAR antibodies. We further discuss recent data from clinical studies that have informed us about the different mechanisms of resistance to anti-BCMA therapies, including antigen escape, BCMA shedding, anti-drug antibodies, T-cell exhaustion, and the emergence of an immunosuppressive microenvironment. This knowledge will be essential to help guide the strategy of serial treatments with anti-BCMA therapies.

scholarly journals CAR T Cells with Enhanced Sensitivity to B Cell Maturation Antigen for the Targeting of B Cell Non-Hodgkin’s Lymphoma and Multiple Myeloma

2018 ◽  
Vol 26 (8) ◽  
pp. 1906-1920 ◽  
Author(s):  
Julia Bluhm ◽  
Elisa Kieback ◽  
Stephen F. Marino ◽  
Felix Oden ◽  
Jörg Westermann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cell ◽  
Hodgkin's Lymphoma ◽  
Cell Maturation ◽  
Car T Cells ◽  
Enhanced Sensitivity ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

scholarly journals Recent updates on CAR T clinical trials for multiple myeloma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Quande Lin ◽  
Juanjuan Zhao ◽  
Yongping Song ◽  
Delong Liu
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cells ◽  
Proteasome Inhibitors ◽  
Car T Cells ◽  
B Cell Maturation ◽  
Car T ◽  
Engineered T Cells ◽  
Glycoprotein Antigen ◽  
History Of

Abstract Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies have dramatically changed the natural history of multiple myeloma (MM). However, most patients eventually suffer a relapse and succumb to the disease. Chimeric antigen receptor (CAR) engineered T cells targeting B cell maturation antigen (BCMA), CD138, CS1 glycoprotein antigen (SLAMF7) and light chains are in active development for therapy of refractory /relapsed (RR) MM. CD19- targeted CAR T cells in conjunction with autologous stem cell transplantation also showed activity in RRMM. Dual- target CAR T cells are in clinical trials for RRMM. This review summarized the recent updates of ongoing CAR T clinical trials for multiple myeloma.

The emergence of b-cell maturation antigen (BCMA) targeting immunotherapy in multiple myeloma

2022 ◽  
pp. 107815522110735
Author(s):  
James A. Davis ◽  
Abigail Shockley ◽  
Hamza Hashmi
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
Efficacy And Safety ◽  
Cell Therapies ◽  
Antibody Drug Conjugates ◽  
Car T Cell ◽  
Drug Conjugates ◽  
B Cell Maturation ◽  
Car T ◽  
Antibody Drug

Objective Multiple myeloma, a plasma cell neoplasm is the second most common hematological malignancy in the United States. Despite significant advances in treatment armamentarium over the last decade, multiple myeloma remains an incurable malignancy. B-cell maturation antigen (BCMA) is an antigen expressed on the surface on plasma cells that can be targeted by novel mechanisms of action including antibody-drug conjugates (ADCs), bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapy. This review summarizes the clinical application and development of approved and investigational immunotherapies targeting BCMA. Data Sources A search of the PubMed database was conducted using the following search terms: BCMA, CAR T, myeloma, belantamab mafodotin, and bispecific. Ongoing clinical trials, as well as abstracts from ASH and ASCO evaluating the efficacy and safety of novel agents targeting BCMA were evaluated. Prescribing information was also reviewed. Data Summary Since the discovery of BCMA as a target for myeloma, researchers have developed antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapies as novel treatment modalities for myeloma patients. Belantamab mafodotin and idecabtagene vicleucel represent currently available therapies and ongoing trials have demonstrated the efficacy and safety of bispecifics and other BCMA targeting therapies. Conclusion BCMA targeting antibody drug conjugates, bispecific T-cell engagers, and CAR T-cell therapies have demonstrated clinical activity in myeloma patients and represent novel therapies in multiple myeloma treatment paradigm.

scholarly journals Emerging agents and regimens for multiple myeloma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yang Yang ◽  
Yi Li ◽  
Huiyao Gu ◽  
Mengmeng Dong ◽  
Zhen Cai
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Clinical Development ◽  
Novel Agents ◽  
Immunomodulatory Drugs ◽  
Car T Cells ◽  
Drug Conjugates ◽  
Car T ◽  
Bite Antibody ◽  
Antibody Drug

Abstract The outcomes of multiple myeloma (MM) have been improved significantly with the therapies incorporating proteasome inhibitors (PI), immunomodulatory drugs, monoclonal antibodies (MoAb) and stem cell transplantation. However, relapsed and refractory MM (RRMM) remains a major challenge. Novel agents and regimens are under active clinical development. These include new PIs such as ixazomib, marizomib, and oprozomib; new MoAbs such as isatuximab and MOR202; novel epigenetic agent ricolinostat and novel cytokines such as siltuximab. Recently, the first XPO-1 inhibitor, selinexor, was approved for RRMM. BCMA-targeted BiTE, antibody–drug conjugates and CAR-T cells have the potential to revolutionize the therapy for RRMM. In this review, we summarized the latest clinical development of these novel agents and regimens.

scholarly journals Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma

2019 ◽  
Vol 116 (19) ◽  
pp. 9543-9551 ◽  
Author(s):  
Jie Xu ◽  
Li-Juan Chen ◽  
Shuang-Shuang Yang ◽  
Yan Sun ◽  
Wen Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cell ◽  
Cell Maturation ◽  
Durable Response ◽  
Hematopoietic Stem ◽  
Car T Cells ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.

scholarly journals BCMA-targeted immunotherapy for multiple myeloma

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Bo Yu ◽  
Tianbo Jiang ◽  
Delong Liu
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Targeted Therapeutics ◽  
Treatment Target ◽  
Drug Conjugates ◽  
B Cell Maturation ◽  
Novel Treatment ◽  
Physiological Properties ◽  
Car T ◽  
Selective Expression

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.

scholarly journals B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma

2019 ◽  
Vol 129 (6) ◽  
pp. 2210-2221 ◽  
Author(s):  
Adam D. Cohen ◽  
Alfred L. Garfall ◽  
Edward A. Stadtmauer ◽  
J. Joseph Melenhorst ◽  
Simon F. Lacey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
T Cells ◽  
B Cell ◽  
Cell Maturation ◽  
Car T Cells ◽  
B Cell Maturation ◽  
Car T ◽  
B Cell Maturation Antigen

scholarly journals Boosting Immunity against Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1221
Author(s):  
Raquel Lopes ◽  
Bruna Velosa Ferreira ◽  
Joana Caetano ◽  
Filipa Barahona ◽  
Emilie Arnault Carneiro ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
Treatment Strategies ◽  
Complete Response ◽  
Drug Conjugates ◽  
Incurable Disease ◽  
Car T ◽  
Patient’S Outcome ◽  
The Impact

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.

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