The development of potential antibody-based therapies for myeloma

• Published in: Blood reviews Vol. 29; no. 2; pp. 81 - 91
• Main Authors: Sherbenou, Daniel W, Behrens, Christopher R, Su, Yang, Wolf, Jeffrey L, Martin, Thomas G, Liu, Bin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2015
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antibody–drug conjugate; Hematology, Oncology and Palliative Medicine; Humans; Immunoconjugates - immunology; Immunoconjugates - therapeutic use; Immunotherapy; Immunotherapy - methods; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - immunology; Multiple Myeloma - therapy; Plasma cell myeloma; Targeted cancer therapy; ASCO; ADC; ALL; CLL; PR; CDC; HL; time to progression; MHC; stable disease; major histocompatibility complex; TNF; overall response rate; T-cell receptor; insulin-like growth factor 1 receptor; LAMP1; Immunotherapy; Fc receptor-like 5; EC50; IMiDs; plasma cell; Targeted cancer therapy; EBMT; human leukocyte antigen; MR; chimeric antigen receptor T-cell; antibody-dependent cellular cytotoxicity; IGF-IR; CAR-T; programmed death 1; Monoclonal antibodies; M-IC; HLA; PD1; monomethyl auristatin F; TCR; Multiple myeloma; American Society of Hematology; ALCL; BM; monomethyl auristatin E; ORR; MFI; SD; TTP; American Society of Clinical Oncology; ASH; antibody–drug conjugate; FcrL5; serum protein electrophoresis; myeloma initiating cells; PD-L1; SLAMF7; very good partial response; anaplastic large cell lymphoma; VGPR; lysosomal-associated membrane protein 1; partial response; ADCC; complement-dependent cytotoxicity; gemtuzumab ozogamicin; Hodgkin lymphoma; MMAE; MMAF; ado-trastuzumab emtansine; half maximal effective concentration; Plasma cell myeloma; GO; minor response; complete response; European Group for Blood and Marrow Transplant; human epidermal growth factor receptor 2; PD1-ligand; signaling lymphocyte activation molecule family member 7; bone marrow; SPEP; CR; mAb; chronic lymphocytic leukemia; median fluorescence intensity; PC; tumor necrosis factor; acute lymphoblastic leukemia; T-DM1; immunomodulatory drugs; HER2; monoclonal antibody; Antibody–drug conjugate
• ISSN: 0268-960X; 1532-1681
• DOI: 10.1016/j.blre.2014.09.011

Abstract With optimal target antigen selection antibody-based therapeutics can be very effective agents for hematologic malignancies, but none have yet been approved for myeloma. Rituximab and brentuximab vedotin are examples of success for the naked antibody and antibody–drug conjugate classes, respectively. Plasma cell myeloma is an attractive disease for antibody-based targeting due to target cell accessibility and the complementary mechanism of action with approved therapies. Initial antibodies tested in myeloma were disappointing. However, recent results from targeting well-characterized antigens have been more encouraging. In particular, the CD38 and CD138 targeted therapies are showing single-agent activity in early phase clinical trials. Here we will review the development pipeline for naked antibodies and antibody–drug conjugates for myeloma. There is clear clinical need for new treatments, as myeloma inevitably becomes refractory to standard agents. The full impact is yet to be established, but we are optimistic that the first FDA-approved antibody therapeutic(s) for this disease will emerge in the near future.