Antibody-drug conjugate therapies in multiple myeloma—what’s next on the horizon?

Abstract

Targeted immunotherapy has arisen over the past decade to the forefront of cancer care. Notably, targeted therapies such as antibody-drug conjugates (ADCs) are becoming more recognized for a novel approach in cancer treatment. The mechanism of action of ADCs incorporates a monoclonal antibody portion directed against the tumor cell antigen and attached to the tumoricidal portion via chemical linkage. The binding of the monoclonal antibody portion allows for tumor cell internalization of the ADC and precise release of the toxic payload within the cancer cell. Multiple myeloma (MM) is an incurable cancer for which belantamab mafodotin was the first-in-class ADC to achieve United States Food and Drug Administration (FDA) approval for treatment of this disease. Clinical trials are currently evaluating other ADCs in the treatment of MM. In this review, a look at the current ADCs being tested in MM clinical trials with a focus on those that are more promising and a potential next-in-line for FDA approval for treatment of MM is discussed.

Multiple Myeloma: A Review of the Literature and a Case Report Highlighting the Immunocompromised State of Myeloma Patients

“…ADCs are composed of a monoclonal antibody, designed to target MM-specific antigens, attached to a therapeutic drug. Upon binding of the antibody to the MM-specific antigen, the complex is internalized by the MM cell and allows for direct delivery of the attached drug [ 24 ]. BiTEs are protein structures composed of two single chain variable fragments, one designed to target MM-specific antigens and the second designed to bind with specific T-cell antigens, usually CD3, connected by a flexible linker.…”

Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche

“…ADCs are targeted immunotherapies composed by a cytotoxic drug fixed to an antibody scaffold directed against a tumor cell antigen. Upon binding with the tumor cell surface antigen, the ADC is internalized by the tumor cell and processed by the endo-lysosomal system leading to the release of the cancer toxic drug ( 182 ). Belantamab mafodotin is the first Food and Drug Administration (FDA)-approved BCMA targeted ADC for treatment of RRMM.…”

Antibody-drug conjugates for lymphoma patients: preclinical and clinical evidences

“…Multiple myeloma-related targets: BCMA, CD38, CD46, CD56, CD74, CD138 ADCs targeting BCMA, CD38, CD46, CD56, CD74, CD138 are not discussed here since this special issue contains another article devoted to ADCs in multiple myeloma [184], and these targets are mainly explored in this disease setting. However, it is important to highlight that the same targets are also expressed in subsets of lymphoma patients, and that the anti-BCMA belantamab mafodotin-blmf is one of the FDA approved ADCs.…”