%0 Journal Article
%T Practical Considerations for Antibodies in Myeloma
%A Faith E. Davies
%A Jacob P. Laubach
%A Joseph Mikhael
%A Niels van de Donk
%J About the Ed Book | ASCO Educational Book
%D 2018
%R https://doi.org/10.1200/EDBK_205443
%X The monoclonal antibodies daratumumab and elotuzumab currently play a prominent role in the management of multiple myeloma (MM). Both have proven to be effective in combination regimens that incorporate other agents with established activity in this disease, and daratumumab monotherapy also has demonstrated great antitumor activity. With the rapid expansion of treatment options for MM in recent years, it is important to understand how best to use daratumumab and elotuzumab in the care of patients with MM. This article aims to provide perspective on this important aspect of MM management through a succinct review of the preclinical and clinical development of daratumumab and elotuzumab, general approaches to management of transplant-eligible and transplant-ineligible patients with MM, determinants of choice of therapy, challenges associated with use of monoclonal antibodies in myeloma, and future directions with monoclonal antibodies in MM. TARGETS OF DARATUMUMAB AND ELOTUZUMAB: CD38 AND SLAMF7 Section: ChooseTop of pageAbstractTARGETS OF DARATUMUMAB AN... <<ANTIBODY-BASED COMBINATIO...CURRENT CLINICAL INDICATI...MONOCLONAL ANTIBODIES IN ...DETERMINANTS OF CHOICE OF...CLINICAL CHALLENGES ASSOC...OTHER COMBINATIONS OF DAR...OTHER CD38- AND SLAMF7-TA...OTHER MYELOMA-TARGETING A...CHIMERIC ANTIGEN RECEPTOR...CONCLUSIONReferences CD38 CD38 is highly and uniformly expressed on MM cells; at relatively low levels on normal lymphoid and myeloid cells; and in some tissues of nonhematopoietic origin, such as prostatic epithelial cells, pancreatic islet cells, and airway-striated muscle.1 CD38 has ectoenzymactic activities and also receptor functions.1 Together, these qualities formed the rationale for the development of CD38 antibodies in MM. The first CD38 antibodies were developed in the early 1990s, but, although these agents had marked anti-MM activity, they were not evaluated in patients with MM.2 The first-in-class therapeutic antibody directed at CD38, daratumumab (fully human immunoglobulin [Ig] G1-kappa), was developed approximately 20 years later.3 Daratumumab was selected from a panel of 42 antibodies because of its marked activity against MM cells via complement-dependent cytotoxicity (CDC). Additional Fc-dependent immune effector mechanisms of daratumumab include antibody-dependent cellular cytotoxicity (ADCC)4 and antibody-dependent cellular phagocytosis (ADCP).5 Furthermore, daratumumab induces programmed cell death via Fc-gamma receptor-mediated cross-linking.6 In addition, modulation of CD38 enzymatic activities may contribute to its anti-MM
%U http://ascopubs.org/doi/full/10.1200/EDBK_205443