Belantamab Mafodotin and Elotuzumab

Patients with RR MM beyond two-three lines of therapy have inferior outcomes. They have to cycle through the available lines of treatment options and ultimately succumb to progressive disease. Despite improvements in modern treatments this subset of MM patients has a grim prognosis and thus represent a population with unmet need. Hence, further advances in combination therapies are required. MM is associated with both qualitative and quantitative T cell dysfunction owing to variety of mechanisms including increased expression of inhibitory immune checkpoint molecules. Elotuzumab enhances NK cell cytotoxicity via SLAMF7 ligation and has an established role in therapy of RR MM in combination with immunomodulatory agents (iMIDs). On the other hand, BCMA has emerged as one of the best therapeutic targets to eradicate plasma cells in MM. Therapeutic success with anti-BCMA ADC belantamab mafodotin is readily evident based on the results of recent trials DREAMM 1 and DREAMM2 in relapsed/refractory MM, leading to its Breakthrough Therapy Designation awarded by US FDA in 2017. Bela has demonstrated the potential to induce immunogenic cell death (ICD) in a BCMA-expressing MM cells. Tumor cells undergoing ICD induced an antigen-specific T cell response, enhancing anti-tumor effects. Generally, in myeloma, success in therapy has always been achieved by multifaceted treatment approach, targeting several pathways concurrently. To combat antigen loss and resistance, combining monoclonal antibodies with different targets is proposed. In this study, we propose immune-stimulatory therapy with anti-SLAMF7 antibody elotuzumab in combination with belantamab mafodotin in subjects with RR MM. Administration of elotuzumab would enrich NK cells and together with belantamab mafodotin would further intensify anti-tumor immunity against MM. This combination would provide a novel all-immune targeted therapy with potentially increased efficacy.

The investigators expect that this unique combination of an antibody drug conjugate and an immune-stimulatory monoclonal antibody, targeting two very relevant pathways in MM will result in significant clinical benefit for patients with RR MM. From the standpoint of safety, each one of these immune-pharmaceutical drugs separately is well-tolerated, and in combination are not expected to display overlapping toxicity. Thus, the investigators believe, the adverse event profile of this combination would be favorable.