EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma

Abstract

This article summarizes the scientific review of daratumumab that led to regulatory approval in the European Union.

Systematic Review on Infusion Reactions to and Infusion Rate of Monoclonal Antibodies Used in Cancer Treatment

“…An Australian expert panel of myeloma nurses suggested a 2-h observation time after the first cycle (28). In addition, patients with a history of severe chronic obstructive pulmonary disease or asthma should receive extra monitoring and be considered for extra postinfusion inhaled medications (corticosteroids and short-and long-acting bronchodilators) (29). Despite the high rate of infusion reactions, one study group in Ohio performed a small open trial on acceleration of the infusion after patients had received two or more doses in 500 ml at the standard infusion rate without complications.…”

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).…”

“…Fifteen patients after 1-3 prior lines (median 2) have been enrolled so far. After a median of 7 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) cycles, current ORR is 87%. Seven patients achieved VGPR and 6 patients PR.…”