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Review
. 2016 Jul;50(7):555-68.
doi: 10.1177/1060028016642786. Epub 2016 Apr 15.

Immunotherapy: A New Approach to Treating Multiple Myeloma with Daratumumab and Elotuzumab

Salma Afifi  1 , Angela Michael  2 , Alexander Lesokhin  3
Affiliations
Review

Immunotherapy: A New Approach to Treating Multiple Myeloma with Daratumumab and Elotuzumab

Salma Afifi et al. Ann Pharmacother. 2016 Jul.

Abstract

Objective: To review the clinical pharmacology, efficacy, and safety of daratumumab and elotuzumab for the treatment of relapsed refractory multiple myeloma (RRMM).

Data sources: A literature search of MEDLINE, PubMed, the US National Institutes of Health Clinicaltrials.gov, the Food and Drug administration, and relevant meeting abstracts was conducted using the terms daratumumab, elotuzumab, multiple myeloma, anti-CD38, HuMax-CD38, HuLuc63, SLAMF7, and anti-CS1 STUDY SELECTION/DATA EXTRACTION: Human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of daratumumab and elotuzumab for MM were identified.

Data synthesis: Daratumumab (anti-CD38) and elotuzumab (anti-CS1) have been recently FDA approved for the treatment of RRMM after showing efficacy in clinical trials. Elotuzumab approval was based on phase III data, and daratumumab gained accelerated approval based on phase I/II trials. Daratumumab has demonstrated significant single-agent activity, with an overall response rate (ORR) of 36% in patients with a median of 4 prior lines of therapy. Elotuzumab has not been shown to have single-agent activity. But the efficacy of both these antibodies in combination with lenalidomide and dexamethasone in RRMM showed an ORR exceeding 80%. Tolerability of elotuzumab and daratumumab seems to be acceptable, with the most common adverse event being infusion reactions.

Conclusion: Daratumumab and elotuzumab have shown encouraging results in RRMM that led to their FDA approval. Both are well tolerated with minimal toxicities. Phase III clinical trials will define optimal combination and place in therapy of daratumumab and elotuzumab.

Keywords: daratumumab; elotuzumab; immunotherapy; monoclonal antibodies; multiple myeloma; refractory; relapsed; treatment.

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Conflict of interest statement

Conflict of interest statement:

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1
Figure 1
Mechanisms of action of daratumumab. Daratumumab can directly induce multiple myeloma cell apoptosis when cross-linked with anti-human immunoglobulin. It can also induce tumor cell killing via Fc-dependent effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADPC) and complement-dependent cytotoxicity (CDC). ADCC is achieved through activation of Fc receptors on myeloid and NK effector cells by tumor cell-attached immunoglobulins. ADCP is mediated by macrophages. CDC is dependent on interaction of the antibody Fc domains with the classic complement-activating protein C1q leading to activation of downstream complement proteins which results in assembly of membrane attack complex (MAC) which creates holes in tumor cell membrane.
See this image and copyright information in PMC

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