Isatuximab: an anti-CD38 therapy that addresses unmet needs and mechanisms of resistance in multiple myeloma.

INTRODUCTION: In recent years, anti-CD38 antibodies have become integral to the multiple myeloma (MM) treatment armamentarium and greatly improved depth of response and patient outcomes. Isatuximab, an anti-CD38 antibody, is approved for both newly diagnosed MM and relapsed/refractory MM. Understanding the distinct mechanistic features of isatuximab within the anti-CD38 drug class provides further insight into treatment selection.

AREAS COVERED: This review discusses the unique mechanism of action of isatuximab, supporting preclinical data, and differentiation from other anti-CD38 antibodies. It will delve into evidence demonstrating the favorable benefit-risk profile of isatuximab in broad patient populations across the MM treatment continuum.

EXPERT OPINION: Isatuximab elicits antitumor activity via multiple tumor-targeting pathways. The direct cytotoxic mechanism of isatuximab is a key differentiator from other anti-CD38 antibodies and translates into clinical benefits in patients with MM. Isatuximab only relies partly on complement-dependent cytotoxicity activity for its antitumor activity, which may have beneficial prognostic implications for patients with 1q21 chromosomal abnormalities and extramedullary disease. This is supported by clinical data, which demonstrate a favorable benefit/risk profile in MM patients including difficult-to-treat patients with poor prognostic outcomes. Further, addition of the novel on-body injector to isatuximab administration modalities may provide advantages over current administration methods.