B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

Abramson, H. N.

doi:10.3390/ijms21155192

Cited by 28 publications

(23 citation statements)

References 164 publications

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“…Investigational BCMA-binding bispecific antibodies include AMG-701, JNJ-7957 (teclistamab), REGN5458, and TNB-383B. [64][65][66][67][68][69] Bispecific antibodies targeting other multiple myeloma antigens-for example, FcRH5 (BFCR4350A, cevostamab) and GPRC5D (JNJ-64407564, talquetamab)have shown promise as well. 67,[70][71][72] Common features of bispecific antibodies include encouraging response rates, often exceeding 60% even in heavily pretreated patients, and generally manageable toxicities.…”

Section: Emerging Immune-based Strategiesmentioning

confidence: 99%

When and How to Treat Relapsed Multiple Myeloma

Nathwani

Bertamini

Banerjee

et al. 2021

American Society of Clinical Oncology Educational Book

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The treatment landscape for relapsed multiple myeloma has expanded considerably in recent years, as numerous agents with new mechanisms of action have been introduced, increasing responses even in advanced disease and prolonging survival. The wealth of novel regimens comes with the challenges of balancing toxicities and aligning a regimen with the biology of the myeloma and the nature of the relapse in conjunction with patient treatment history and personal preference. Herein, we provide an overview of treatment options for both early and late relapsing disease as well as a discussion of the role of emerging immune-based therapies.

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Section: Emerging Immune-based Strategiesmentioning

confidence: 99%

When and How to Treat Relapsed Multiple Myeloma

Nathwani

Bertamini

Banerjee

et al. 2021

American Society of Clinical Oncology Educational Book

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“…Although utilization of CD19 as a suitable binding partner for bi-specific antibodies in MM appears to be stymied at this point, BCMA, as in the ADC arena, has assumed a major role in BiTE ® research. [153][154][155][156] One such agent, AMG 420 (BI-836909) demonstrated favorable results in a phase I doseescalation trial (NCT02514239), achieving a 31% ORR in 42 RRMM patients, including 70% (7/10) in those who received the maximum tolerated dose (400 mg/day). Infections and polyneuropathy were the most serious adverse events related to treatment.…”

Section: T-cell-engaging Bi-specific Antibodiesmentioning

confidence: 99%

Immunotherapy of Multiple Myeloma: Promise and Challenges

Abramson

2021

ITT

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Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how the disease is treated. The picture changed dramatically once again starting with the 2015 FDA approval of two monoclonal antibodies (mAbs) – the anti-CD38 daratumumab and the anti-SLAMF7 elotuzumab. Daratumumab, in particular, has had a great impact on MM therapy and today is often included in various regimens to treat the disease, both in newly diagnosed cases and in the relapse/refractory setting. Recently, other immunotherapies have been added to the arsenal of drugs available to fight this malignancy. These include isatuximab (also anti-CD38) and, in the past year, the antibody-drug conjugate (ADC) belantamab mafodotin and the chimeric antigen receptor (CAR) T-cell product idecabtagene vicleucel (ide-cel). While the accumulated benefits of these newer agents have resulted in a doubling of the disease’s five-year survival rate to more than 5 years and improved quality of life, the disease remains incurable. Almost without exception patients experience relapse and/or become refractory to the drugs used, making the search for innovative therapies all the more essential. This review covers the current scope of anti-myeloma immunotherapeutic agents, both those in clinical use and on the horizon, including naked mAbs, ADCs, bi- and multi-targeted mAbs, and CAR T-cells. Emphasis is placed on the benefits of each along with the challenges that need to be overcome if MM is to be considered curable in the future.

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“…Other studies with Belantamab Mafodotin either as single-agent or in combination with other drugs are currently ongoing. Moreover, many others anti-BCMA mAbs drug conjugate are in clinical development [96].…”

Section: Anti-bcma Targeting Antibodiesmentioning

confidence: 99%

Novel Approaches to Improve Myeloma Cell Killing by Monoclonal Antibodies

Storti

Costa

Marchica

et al. 2020

JCM

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The monoclonal antibodies (mAbs) have significantly changed the treatment of multiple myeloma (MM) patients. However, despite their introduction, MM remains an incurable disease. The mAbs currently used for MM treatment were developed with different mechanisms of action able to target antigens, such as cluster of differentiation 38 (CD38) and SLAM family member 7 (SLAMF7) expressed by both, MM cells and the immune microenvironment cells. In this review, we focused on the mechanisms of action of the main mAbs approved for the therapy of MM, and on the possible novel approaches to improve MM cell killing by mAbs. Actually, the combination of anti-CD38 or anti-SLAMF7 mAbs with the immunomodulatory drugs significantly improved the clinical effect in MM patients. On the other hand, pre-clinical evidence indicates that different approaches may increase the efficacy of mAbs. The use of trans-retinoic acid, the cyclophosphamide or the combination of anti-CD47 and anti-CD137 mAbs have given the rationale to design these types of combinations therapies in MM patients in the future. In conclusion, a better understanding of the mechanism of action of the mAbs will allow us to develop novel therapeutic approaches to improve their response rate and to overcome their resistance in MM patients.

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B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

Cited by 28 publications

References 164 publications

When and How to Treat Relapsed Multiple Myeloma

When and How to Treat Relapsed Multiple Myeloma

Immunotherapy of Multiple Myeloma: Promise and Challenges

Novel Approaches to Improve Myeloma Cell Killing by Monoclonal Antibodies

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