Targeting BCMA in Multiple Myeloma: Advances in Antibody-Drug Conjugate Therapy

SIMPLE SUMMARY: Despite the variety of drugs used to treat multiple myeloma and the ever-lengthening survival times, a recurring problem is that many current drugs affect healthy cells, causing side effects, additional illnesses, and drug intolerances. In theory, antibody-drug conjugates targeting deliberately chosen antigens can deliver drugs directly to cancer cells with minimal damage to healthy cells. As such, the conjugates targeting the B cell maturation antigen, which is restrictively expressed on malignant plasma cells, are an active area of research. Several of them are currently in clinical trials to test their safety and efficacy, both alone and in combination with other therapies. The findings will provide better treatment options for multiple myeloma patients. ABSTRACT: Multiple myeloma (MM) is an incurable cancer of the plasma cells. In the last twenty years, treatment strategies have evolved toward targeting MM cells—from the shotgun chemotherapy approach to the slightly more targeted approach of disrupting important MM molecular pathways to the immunotherapy approach that specifically targets MM cells based on protein expression. Antibody-drug conjugates (ADCs) are introduced as immunotherapeutic drugs which utilize an antibody to deliver cytotoxic agents to cancer cells distinctively. Recent investigations of ADCs for MM treatment focus on targeting B cell maturation antigen (BCMA), which regulates B cell proliferation, survival, maturation, and differentiation into plasma cells (PCs). Given its selective expression in malignant PCs, BCMA is one of the most promising targets in MM immunotherapy. Compared to other BCMA-targeting immunotherapies, ADCs have several benefits, such as lower price, shorter production period, fewer infusions, less dependence on the patient’s immune system, and they are less likely to over-activate the immune system. In clinical trials, anti-BCMA ADCs have shown safety and remarkable response rates in patients with relapsed and refractory MM. Here, we review the properties and clinical applications of anti-BCMA ADC therapies and discuss the potential mechanisms of resistance and ways to overcome them.