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Emerging Multiple Myeloma Therapies: mAbs, ADCs, CAR-T Cells & Bispecific Antibodies
EP39125
Poster Title: Emerging Multiple Myeloma Therapies: mAbs, ADCs, CAR-T Cells & Bispecific Antibodies
Submitted on 09 Aug 2022
Author(s): Sonia Li
Affiliations: Biopharma PEG Scientific Inc.
Poster Views: 140
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Poster Information
Abstract: Multiple myeloma (MM) is a malignant proliferation of plasma cells (PCs) that produces excess monoclonal immunoglobulins, resulting in a series of clinical manifestations including extensive bone destruction, recurrent infections, anemia, hypercalcemia, hyperviscosity syndrome and renal insufficiency.

Although multiple myeloma remains an incurable disease, the 5-year relative survival rate has nearly doubled in the last 20 years, from 32.1% in 1996 to 54.9% in 2016, according to the National Cancer Institute. Over the past 5-10 years, numerous treatment options have entered the myeloma treatment arena, greatly extending progression-free survival (PFS) and overall survival (OS). The focus of research has shifted from systemic therapies such as chemotherapy to more specific targeted therapies such as immunotherapy. A variety of innovative targeted therapies that are effective against multiple myeloma, such as monoclonal antibodies (mAbs), CAR-T cell therapy, antibody-drug conjugates(ADCs), and bispecific antibodies, have made rapid progress.

Mechanisms of action of emerging multiple myeloma therapies
Figure 1. Mechanisms of action of emerging multiple myeloma therapies, Source: reference 1

Monoclonal Antibodies (mAbs)
The first immunotherapies approved for use in patients with multiple myeloma are the monoclonal antibodies Daratumumab (Darzalex) and Elotuzumab (Empliciti). The third monoclonal antibody, Isatuximab (Sarclisa), was approved for relapsed refractory multiple myeloma in March 2020.

Drug Target Company Approval Date
Daratumumab CD38 Johnson & Johnson/Genmab Nov 2015(FDA)
Elotuzumab SLAMF7 BMS/AbbVie Nov 2015(FDA)
Isatuximab CD38 Sanofi Mar 2020 (FDA)
Table 1. FDA Approved monoclonal antibodies for multiple myeloma
Daratumumab
Daratumumab, a humanized, anti-CD38 IgG1 monoclonal antibody developed by Johnson & Johnson in collaboration with Genmab, binds to CD38 expressed by tumor cells and induces apoptosis through various immune-related mechanisms, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as Fcγ receptors.

Unlike traditional targeted drugs, Daratumumab is the first monoclonal antibody drug that directly targets the CD38 protein on multiple myeloma cells. In November 2015, Daratumumab was approved for marketing by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma in people who had received at least three prior therapies.

Elotuzumab
Elotuzumab is a monoclonal antibody developed by Bristol-Myers Squibb (BMS) and AbbVie that targets the cell surface protein SLAMF7, which is found in both multiple myeloma cells and natural killer (NK) cells. It provides a dual attack on cancer by directly targeting multiple myeloma cells and enhancing the ability of NK cells to kill them. The drug did not have significant activity alone in the treatment of relapsed/refractory multiple myeloma, but when combined with other antitumor agents, such as bortezomib or lenalidomide, the antimyeloma activity was significant, improving patient response rates and clinical prognosis. Elotuzumab was approved for marketing by the FDA on November 30, 2015, and was used in combination with lenalidomide and dexamethasone in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma with one to three prior treatments.

Isatuximab
Isatuximab, an IgG1 chimeric monoclonal antibody developed by Sanofi, targets a specific epitope of the plasma cell CD38 receptor and is able to trigger a variety of unique mechanisms of action, including promotion of programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is expressed at high levels on multiple myeloma cells and is a cell surface receptor target for antibody therapy in multiple myeloma and other malignancies.

Isatuximab has been granted orphan drug status for the treatment of relapsed/refractory multiple myeloma in both the United States and the European Union. Currently, related studies are also evaluating the potential of Isatuximab in other hematologic malignancies and solid tumors. On March 2, 2020, the U.S. FDA approved Isatuximab in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
Summary: A variety of innovative targeted therapies are effective against multiple myeloma, such as monoclonal antibodies (mAbs), CAR-T cell therapy, ADCs, and bispecific antibodies, have made rapid progress.References: Biopharma PEG provides GMP standard PEG derivatives and bulk orders via custom synthesis, offering the opportunity to match customers' special quality requirements. ADC linkers with molecular weights, branching, and functional groups not listed in our online catalog may be available by custom synthesis.Report abuse »
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