The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

SIMPLE SUMMARY: The introduction of monoclonal antibodies (moAbs) has dramatically improved outcomes in multiple myeloma (MM). Their high clinical efficacy and safe adverse risk profile have made moAbs a first choice in relapsed MM and have led to the introduction of moAbs into the standard upfront regimen in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). Yet, the majority of patients will eventually relapse and patients who become refractory to moAbs, IMiDs and PIs have dismal outcomes and are in dire need of agents with novel mechanisms. Bispecific antibody (bsAb) and chimeric antigen receptor T cells (CAR T) have emerged as potent single agents in this heavily pretreated and refractory patient population and clinical trials to test their efficacy in earlier disease are upcoming. There is great enthusiasm that the optimization of bsAbs, CAR T cells and moAbs will lead to sustained remission and a possible cure in MM in the near future. ABSTRACT: Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients. Over the past decade, we have witnessed the “era of monoclonal antibody (moAb)”, setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal outcome. Emerging T-cell directing therapies, such as bispecific antibody (bsAb) and chimeric antigen receptor T cells (CAR T) have shown unprecedented responses and outcomes in these heavily pretreated and treatment-refractory patients. Their clinical efficacy combined with high tolerability will likely lead to the use of these agents earlier in the treatment course and there is great enthusiasm that a combination of T cell directed therapy with moAbs can lead to long duration remission in the near future, possibly even without the need of high dose chemotherapy and stem cell transplantation. Herein, we summarize the role of naked moAbs in MM in the context of newer immunotherapeutic agents like bsAb and CAR T therapy.