What is the role of Daratumumab (Darzalex), Ixazomib (Ninlaro), and Elotuzumab (Empliciti) in the treatment of multiple myeloma (MM)?

Updated: Sep 30, 2019
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

The following three new drugs were approved in November 2015:

  • Daratumumab (Darzalex)
  • Ixazomib (Ninlaro)
  • Elotuzumab (Empliciti)

Daratumumab gained approval from the FDA for patients with MM who had received at least three prior treatments, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or whose disease is refractory to both a PI and an IMiD. The approval was based on the phase II MMY2002 (SIRIUS) study that showed treatment with single-agent daratumumab resulted in an ORR of 29.2% in patients who received a median of five prior lines of therapy, including a PI and an IMiD. [84]

Stringent complete response (sCR) was reported in 2.8%, very good partial response (VGPR) was reported in 9.4%, and partial response (PR) was reported in 17% of patients. For responders, the median duration of response was 7.4 months. At baseline, 97% of patients were refractory to their last line of therapy, 95% were refractory to both a PI and an IMiD, and 77% were refractory to alkylating agents. [84] These data are supported by similar results from a phase I/II trial. [85]

Ixazomib is a reversible proteasome inhibitor. It preferentially binds and inhibits the chymotrypsinlike activity of the beta 5 subunit of the 20S proteasome. Ixazomib is indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy. Approval was based on data from the phase 3 TOURMALINE-MM1 trial, an international, randomized, double-blind clinical trial of 722 patients with treatment-refractory or recurrent multiple myeloma. It compared ixazomib with placebo the patients who also received lenalidomide and dexamethasone. Median progression-free survival was improved by 35% with ixazomib compared with placebo (20.6 vs 14.7 months; P = 0.012). [86]

Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (signaling lymphocytic activation molecule family member 7) protein. SLAMF7 is expressed on myeloma cells and natural killer cells and plasma cells. Elotuzumab facilitates the interaction with natural killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity. It is indicated for use in combination with lenalidomide and dexamethasone for MM in patients who have received 1-3 prior therapies.

Approval was based on the ELOQUENT-2 trial, a randomized, open-label clinical study that included 646 participants with multiple myeloma who had experienced relapse or who had not responded to previous treatment. The addition of elotuzumab to the combination of lenalidomide and dexamethasone extended progression- free survival to 19.4 months, as compared with 14.9 months seen in patients treated with lenalidomide and dexamethasone (P< 0.001). Additionally, the overall response rate (including complete and partial responses) was 78.5%, compared with 60.1% in patients receiving lenalidomide and dexamethasone (P< 0.001). [87]

The ELOQUENT-3 trial studies 117 patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor. Patients received elotuzumab plus pomalidomide and dexamethasone or pomalidomide and dexamethasone alone (control group). Median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The overall response rate was 53% in the elotuzumab group compared with 26% in the control group. [88]


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