INTRODUCTION
death
DISEASE, MYELOMA, MULTIPLE MYELOMA (MM), SOLID TUMORS
Despite the advent of novel treatments over the past decade, multiple myeloma (MM) remains incurable and patients face multiple lines of therapy due to the relapsing and refractory nature of the disease. Antibodies that target CD38, a glycoprotein that is uniformly expressed on myeloma cells and plays important roles in immune‐system evasion,Isatuximab (Sarclisa®) is an immunoglobulin (Ig)G1 monoclonal antibody (mAb) that targets a specific epitope of CD38 and contributes to myeloma cell killing via multiple mechanisms of action.Based on studies in patients with RRMM showing clinical response with single‐agent isatuximab, which is enhanced in combination with immunomodulatory drugs (IMiDs), a rationale supports the combination of anti‐CD38 antibodies with other potentially synergistic immunomodulators.Anti‐PD‐1 antibodies play a clear role in the treatment of various solid tumors, but their role in the treatment of MM has not been fully elucidated. As a single agent, the anti‐PD‐1 agent nivolumab showed minimal activity in a Phase 1 trial of 17 patients with RRMM, yielding a stable disease rate of 63%. Partial responses or better were not seen, with the exception of one complete response occurring after local radiation therapy.The goal of this study was to determine whether cemiplimab may enhance the anti‐myeloma activity of isatuximab. This phase 1/2 trial (NCT03194867) is the first study of isatuximab plus cemiplimab designed to evaluate safety, tolerability, efficacy, and pharmacokinetics of the combination in RRMM. Due to previous Food and Drug Administration alerts on safety concerns with increasing risk of death regarding combinations of anti‐PD‐1/PD‐L1 agents with immunomodulatory agents (i.e., pomalidomide, lenalidomide) in the treatment of MM,