Potential role of daratumumab in the treatment of multiple myeloma

Abstract

Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA), a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma.

Minimal Residual Disease Assessment in the Context of Multiple Myeloma Treatment

“…Figure 1 shows some representative aberrant immunophenotype of neoplastic plasma cells. The development and use of therapeutic anti-CD38 antibodies, such as daratumumab [ 22 ], which could reduce the expression of CD38 on the plasma cells, has also made it necessary to search for alternative markers for the identification of normal or neoplastic plasma cells. CD269, CD319, CD229, and CD54 have been found to be valuable for this purpose.…”

Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry

“…139 Even though the discovery of these mAb therapies offer a new avenue by which we can approach the detection of multiple myeloma, they have made the search for alternative markers to identify both normal and neoplastic PCs by MFC a priority. 140 Independent investigators have reported the expression of CD54, CD229, CD269, and CD319 to be valuable for this purpose. 54,141,142 In particular, CD269 and CD319 were found to be more versatile markers and withstood storage longer than CD138.…”

Refractory IgD Multiple Myeloma Treated with Daratumumab: A Case Report and Literature Review

“…Daratumumab, an IgG1-k fully human anti-CD38 monoclonal antibody, exerts its cytotoxic effect through a number of mechanisms after binding to CD38, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated phagocytosis (ADCP), and the direct induction of apoptosis [ 12 , 13 ]. Moreover, an immunomodulatory effect of daratumumab was also recently described [ 14 ]. The safety of daratumumab was investigated in a dose-escalation phase I/II trial of 104 patients with relapsed or refractory multiple myeloma.…”