Daratumumab in multiple myeloma

Abstract

The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.

Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

“…Slowing down the infusion rate of the drug also controlled symptoms. More severe reported AEs included pneumonia, thrombocytopenia, neutropenia, and anemia, in less than 5% of patients …”

“…More severe reported AEs included pneumonia, thrombocytopenia, neutropenia, and anemia, in less than 5% of patients. 15,16 We used the recommended dose of 16 mg/kg, which was determined as the effective dose based on findings from previous studies on patients with multiple myeloma. 5 It is possible that a reduced dose would suffice in nonmalignant cases such as ours, but given the favorable safety profile of the drug we opted to use the full effective dose.…”

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses

“…Daratumumab is a first-in-class, fully humanized IgG1-k MoAb, with a high affinity to CD38 [9,10]. Daratumumab induces cellular death through various mechanisms, primarily resulting from Fc-dependent processes, such as antibodydependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).…”

“…Daratumumab is the first anti-CD38 MoAb approved for MM [9,10] based on two-phase 1-2 trials (GEN501, NCT00574288, and SIRIUS, NCT01985126) [13,14], subsequently updated in a pooled analysis of 148 patients treated at the final, optimal dose of 16 mg/kg [15]. These last patients had received a median of 5 prior lines of therapy (range 2 to 14) and 86.5% of them were double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMID).…”

“…Lakshman et al, retrospectively reviewed the outcomes of 126 patients with RRMM, 33% with high-cytogenetic risk, and 13% refractory to single-agent daratumumab, who had received at least one cycle of daratumumab-based combination therapies [45]. Median number of prior therapies was 4 (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. ORR/at least VGPR rates in the DPd, DRd, DVd and other DCT groups were 46/16%, 50/29%, 57/14%%, and 35/18%, respectively (P = 0.33).…”