BCMA-targeting approaches for treatment of multiple myeloma.

Recent advances in treatment modalities have led to improved survival in patients with multiple myeloma (MM). However, despite these, MM remains an incurable disease. Many MM patients relapse through and become refractory to current treatment strategies or are intolerant due to toxicities arising from therapy. As such, novel strategies addressing new targets are crucial in improving care for MM patients. BCMA has emerged as a rationale therapeutic target for treatment of MM as it is preferentially expressed in mature B-lymphocytes and plasma cells with the overexpression and activation of BCMA via its ligands associated with the disease progression in multiple myeloma. Given the high expression of BCMA in malignant Plasma cells compared to those from normal healthy volunteers, targeting BCMA should reduce risks of on-target off-tumor toxicities. The main BCMA-targeting approaches currently used for treatment of MM include: 1) chimeric antigen receptor (CAR) T-cell therapy; 2) bi- and multi- specific antibodies; and 3) monoclonal antibodies and their drug conjugates. This review will outline these therapeutic agents and present their emerging clinical data.

Current and future perspectives of maintenance therapy in multiple myeloma.

While the outcome of patients with multiple myeloma has significantly improved over the last two decades, the disease remains incurable for the majority of patients. With the advent of novel agents, there has been a shift towards prolonged therapy as opposed to fixed-duration therapy, aimed at improving progression-free survival and overall survival. Evidence favoring continuous therapy has emerged over the last 2 decades and in the context of maintenance after proteasome inhibitor plus immunomodulatory drug induction followed by high dose melphalan and stem cell transplantation, this leads to >80% overall survival at 5 years. Maintenance therapy specifically has been demonstrated to correlate with increasing depth of disease response with a significant proportion of patients who remain minimal residual disease positive at the end of induction therapy achieving minimal residual disease negativity with maintenance therapy both in clinical trials and selected real world populations. As the survival improves, it is crucial to identify patients who are projected to have better survival and spare them toxicities arising from indefinite maintenance therapy. The role of minimal residual disease in this context is being investigated in numerous clinical trials and in the next few years the goal should be to use this in a rational way to achieve the ability to identify patients who would require continuation or escalation of therapy to improve their projected survival as well as to identify the group of patients in whom maintenance therapy could perhaps be time-limited without compromising their survival. Here we review the evidence for maintenance therapy from the key trials in the past years, present an overview of the current landscape and our perspective of maintenance therapy in the future.