Monoclonal antibodies targeting CD38 in hematological malignancies and beyond

Niels W C J van de Donk, Maarten L Janmaat, Tuna Mutis, Jeroen J Lammerts van Bueren, Tahamtan Ahmadi, A Kate Sasser, Henk M Lokhorst, Paul W H I Parren, Niels W C J van de Donk, Maarten L Janmaat, Tuna Mutis, Jeroen J Lammerts van Bueren, Tahamtan Ahmadi, A Kate Sasser, Henk M Lokhorst, Paul W H I Parren

Abstract

CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti-tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38-targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody-mediated autoimmune diseases.

Keywords: CD38; cancer; daratumumab; isatuximab; multiple myeloma; therapeutic antibody.

© 2016 Genmab, Utrecht, the Netherlands. Immunological Reviews published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Mechanisms of action of daratumumab.
Figure 2
Figure 2
Daratumumab modulates the enzymatic activity of CD38. (A, B) Concentration‐dependent inhibition of CD38 cyclase activity by daratumumab tested on recombinant CD38 protein (A) or CHO cells stably transfected with human CD38 (B). Therefore, recombinant CD38 protein or CHO‐CD38 cells were incubated with daratumumab and NGD, and the presence of fluorescent cGDPR in supernatant was measured. The graphs show the % inhibition in cGDPR production compared to the untreated controls. (C) Enzymatic processing of NAD and NADP by CD38 and modulation of this activity by daratumumab.
Figure 3
Figure 3
Resolving interference of daratumumab in the indirect antiglobulin test (IAT). (A, B) Daratumumab in the patient's serum binds to the test RBCs. After adding the anti‐IgG reagent, RBC agglutination is observed, thereby generating a false‐positive result (A) or masking the presence of irregular antibodies (B). (C, D) Daratumumab‐specific anti‐idiotype antibodies are added to the patient's serum and bind to daratumumab (1). Alternatively, test RBCs are treated with DTT, resulting in denaturation of CD38 and loss of daratumumab binding (2). If the patient has no irregular antibodies, binding of daratumumab to RBCs is blocked generating a negative IAT test result. However, if the serum contains irregular antibodies, binding of these antibodies to RBC will result in a true positive IAT test result.

References

    1. Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T‐cell lineage. Proc Natl Acad Sci USA 1980;77:1588–1592.
    1. Katz F, et al. Chromosome assignment of monoclonal antibody‐defined determinants on human leukemic cells. Eur J Immunol 1983;13:1008–1013.
    1. Ferrero E, Malavasi F. Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+‐converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP‐ribosyl cyclase. J Immunol 1997;159:3858–3865.
    1. Kosco‐Vilbois MH. Are follicular dendritic cells really good for nothing? Nat Rev Immunol 2003;3:764–769.
    1. Musso T, et al. CD38 expression and functional activities are up‐regulated by IFN‐gamma on human monocytes and monocytic cell lines. J Leukoc Biol 2001;69:605–612.
    1. Kishimoto H, et al. Molecular mechanism of human CD38 gene expression by retinoic acid. Identification of retinoic acid response element in the first intron. J Biol Chem 1998;273:15429–15434.
    1. Song EK, et al. NAADP mediates insulin‐stimulated glucose uptake and insulin sensitization by PPARgamma in adipocytes. Cell Rep 2012;2:1607–1619.
    1. Drach J, Zhao S, Malavasi F, Mehta K. Rapid induction of CD38 antigen on myeloid leukemia cells by all trans‐retinoic acid. Biochem Biophys Res Commun 1993;195:545–550.
    1. Mehta K, McQueen T, Manshouri T, Andreeff M, Collins S, Albitar M. Involvement of retinoic acid receptor‐alpha‐mediated signaling pathway in induction of CD38 cell‐surface antigen. Blood 1997;89:3607–3614.
    1. Saborit‐Villarroya I, et al. E2A is a transcriptional regulator of CD38 expression in chronic lymphocytic leukemia. Leukemia 2011;25:479–488.
    1. Ferrero E, Saccucci F, Malavasi F. The human CD38 gene: polymorphism, CpG island, and linkage to the CD157 (BST‐1) gene. Immunogenetics 1999;49:597–604.
    1. Jackson DG, Bell JI. Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation. J Immunol 1990;144:2811–2815.
    1. Lee HC, Aarhus R. ADP‐ribosyl cyclase: an enzyme that cyclizes NAD+ into a calcium‐mobilizing metabolite. Cell Regul 1991;2:203–209.
    1. States DJ, Walseth TF, Lee HC. Similarities in amino acid sequences of aplysia ADP‐ribosyl cyclase and human lymphocyte antigen CD38. Trends Biochem Sci 1992;17:495.
    1. Malavasi F, Funaro A, Roggero S, Horenstein A, Calosso L, Mehta K. Human CD38: a glycoprotein in search of a function. Immunol Today 1994;15:95–97.
    1. Liu Q, Kriksunov IA, Graeff R, Munshi C, Lee HC, Hao Q. Crystal structure of human CD38 extracellular domain. Structure 2005;13:1331–1339.
    1. Bruzzone S, Guida L, Franco L, Zocchi E, Corte G, De Flora A. Dimeric and tetrameric forms of catalytically active transmembrane CD38 in transfected HeLa cells. FEBS Lett 1998;433:275–278.
    1. Franco L, Guida L, Bruzzone S, Zocchi E, Usai C, De Flora A. The transmembrane glycoprotein CD38 is a catalytically active transporter responsible for generation and influx of the second messenger cyclic ADP‐ribose across membranes. FASEB J 1998;12:1507–1520.
    1. Mallone R, et al. Characterization of a CD38‐like 78‐kilodalton soluble protein released from B cell lines derived from patients with X‐linked agammaglobulinemia. J Clin Invest 1998;101:2821–2830.
    1. Hara‐Yokoyama M, et al. Tetrameric interaction of the ectoenzyme CD38 on the cell surface enables its catalytic and raft‐association activities. Structure 2012;20:1585–1595.
    1. Funaro A, et al. Identification and characterization of an active soluble form of human CD38 in normal and pathological fluids. Int Immunol 1996;8:1643–1650.
    1. Dianzani U, et al. Interaction between endothelium and CD4+CD45RA+ lymphocytes. Role of the human CD38 molecule. J Immunol 1994;153:952–959.
    1. Deaglio S, et al. Human CD38 ligand. A 120‐KDA protein predominantly expressed on endothelial cells. J Immunol 1996;156:727–734.
    1. Deaglio S, et al. Human CD38 (ADP‐ribosyl cyclase) is a counter‐receptor of CD31, an Ig superfamily member. J Immunol 1998;160:395–402.
    1. Newman PJ, et al. PECAM‐1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science 1990;247:1219–1222.
    1. Fernandez JE, et al. Analysis of the distribution of human CD38 and of its ligand CD31 in normal tissues. J Biol Regul Homeost Agents 1998;12:81–91.
    1. Cesano A, Visonneau S, Deaglio S, Malavasi F, Santoli D. Role of CD38 and its ligand in the regulation of MHC‐nonrestricted cytotoxic T cells. J Immunol 1998;160:1106–1115.
    1. Mehta K, Malavasi F. Human CD38 and Related Molecules. Basel: Karger, SAG, 2000.
    1. Howard M, et al. Formation and hydrolysis of cyclic ADP‐ribose catalyzed by lymphocyte antigen CD38. Science 1993;262:1056–1059.
    1. Cockayne DA, et al. Mice deficient for the ecto‐nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood 1998;92:1324–1333.
    1. Chini EN, Chini CC, Kato I, Takasawa S, Okamoto H. CD38 is the major enzyme responsible for synthesis of nicotinic acid‐adenine dinucleotide phosphate in mammalian tissues. Biochem J 2002;362:125–130.
    1. Takasawa S, et al. Synthesis and hydrolysis of cyclic ADP‐ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP. J Biol Chem 1993;268:26052–26054.
    1. Aarhus R, Graeff RM, Dickey DM, Walseth TF, Lee HC. ADP‐ribosyl cyclase and CD38 catalyze the synthesis of a calcium‐mobilizing metabolite from NADP. J Biol Chem 1995;270:30327–30333.
    1. Guse AH, et al. Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP‐ribose. Nature 1999;398:70–73.
    1. Matsuoka T, et al. Expression of CD38 gene, but not of mitochondrial glycerol‐3‐phosphate dehydrogenase gene, is impaired in pancreatic islets of GK rats. Biochem Biophys Res Commun 1995;214:239–246.
    1. Takasawa S, Nata K, Yonekura H, Okamoto H. Cyclic ADP‐ribose in insulin secretion from pancreatic beta cells. Science 1993;259:370–373.
    1. Kato I, Yamamoto Y, Fujimura M, Noguchi N, Takasawa S, Okamoto H. CD38 disruption impairs glucose‐induced increases in cyclic ADP‐ribose, [Ca2+]i, and insulin secretion. J Biol Chem 1999;274:1869–1872.
    1. Morandi F, et al. CD56brightCD16‐ NK cells produce adenosine through a CD38‐mediated pathway and act as regulatory cells inhibiting autologous CD4+ T cell proliferation. J Immunol 2015;195:965–972.
    1. Karakasheva TA, et al. CD38‐expressing myeloid‐derived suppressor cells promote tumor growth in a murine model of esophageal cancer. Cancer Res 2015;75:4074–4085.
    1. Deaglio S, Mehta K, Malavasi F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk Res 2001;25:1–12.
    1. Zocchi E, et al. A single protein immunologically identified as CD38 displays NAD+ glycohydrolase, ADP‐ribosyl cyclase and cyclic ADP‐ribose hydrolase activities at the outer surface of human erythrocytes. Biochem Biophys Res Commun 1993;196:1459–1465.
    1. Lee HC, Zocchi E, Guida L, Franco L, Benatti U, De Flora A. Production and hydrolysis of cyclic ADP‐ribose at the outer surface of human erythrocytes. Biochem Biophys Res Commun 1993;191:639–645.
    1. Ramaschi G, Torti M, Festetics ET, Sinigaglia F, Malavasi F, Balduini C. Expression of cyclic ADP‐ribose‐synthetizing CD38 molecule on human platelet membrane. Blood 1996;87:2308–2313.
    1. Cyster JG. Homing of antibody secreting cells. Immunol Rev 2003;194:48–60.
    1. Lee HC, Aarhus R. Wide distribution of an enzyme that catalyzes the hydrolysis of cyclic ADP‐ribose. Biochim Biophys Acta 1993;1164:68–74.
    1. Kestens L, et al. Expression of activation antigens, HLA‐DR and CD38, on CD8 lymphocytes during HIV‐1 infection. AIDS 1992;6:793–797.
    1. Ho HN, et al. Circulating HIV‐specific CD8+ cytotoxic T cells express CD38 and HLA‐DR antigens. J Immunol 1993;150:3070–3079.
    1. Henriques A, et al. CD38, CD81 and BAFFR combined expression by transitional B cells distinguishes active from inactive systemic lupus erythematosus. Clin Exp Med 2015. doi:.
    1. Sun L, et al. CD38/ADP‐ribosyl cyclase: a new role in the regulation of osteoclastic bone resorption. J Cell Biol 1999;146:1161–1172.
    1. Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 2004;121:482–488.
    1. Damle R. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999;94:1840–1847.
    1. Konoplev S, Medeiros LJ, Bueso‐Ramos CE, Jorgensen JL, Lin P. Immunophenotypic profile of lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. Am J Clin Pathol 2005;124:414–420.
    1. Perfetti V, et al. AL amyloidosis. Characterization of amyloidogenic cells by anti‐idiotypic monoclonal antibodies. Lab Invest 1994;71:853–861.
    1. Parry‐Jones N, et al. Cytogenetic abnormalities additional to t(11;14) correlate with clinical features in leukaemic presentation of mantle cell lymphoma, and may influence prognosis: a study of 60 cases by FISH. Br J Haematol 2007;137:117–124.
    1. Keyhani A, et al. Increased CD38 expression is associated with favorable prognosis in adult acute leukemia. Leuk Res 2000;24:153–159.
    1. Marinov J, Koubek K, Stary J. Immunophenotypic significance of the lymphoid Cd38 antigen in myeloid blood malignancies. Neoplasma 1993;40:355–358.
    1. Suzuki R, et al. Aggressive natural killer‐cell leukemia revisited: large granular lymphocyte leukemia of cytotoxic NK cells. Leukemia 2004;18:763–770.
    1. Wang L, et al. CD38 expression predicts poor prognosis and might be a potential therapy target in extranodal NK/T cell lymphoma, nasal type. Ann Hematol 2015;94:1381–1388.
    1. van de Donk NW, Lokhorst HM, Anderson KC, Richardson PG. How I treat plasma cell leukemia. Blood 2012;120:2376–2389.
    1. Kumar SK, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia 2014;28:1122–1128.
    1. van de Donk NW, Sonneveld P. Diagnosis and risk stratification in multiple myeloma. Hematol Oncol Clin North Am 2014;28:791–813.
    1. Lonial S, Durie B, Palumbo A, Miguel JS. Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives. Leukemia 2015. doi:.
    1. de Weers M, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 2011;186:1840–1848.
    1. Deckert J, et al. SAR650984, a novel humanized CD38‐targeting antibody, demonstrates potent antitumor activity in models of multiple myeloma and other CD38+ hematologic malignancies. Clin Cancer Res 2014;20:4574–4583.
    1. Park PU, et al. WO2008/047242: Novel Anti‐CD38 Antibodies for the Treatment of Cancer. 2008.
    1. Elias KA, et al. WO2012/092612: Anti‐CD38 Antibodies. 2012.
    1. Chu SY, et al. Immunotherapy with long‐lived anti‐CD38× anti‐CD3 bispecific antibodies stimulates potent T cell‐mediated killing of human myeloma cell lines and CD38+ cells in monkeys: a potential therapy for multiple myeloma. Blood 2014;124:4727.
    1. Lonberg N, et al. Antigen‐specific human antibodies from mice comprising four distinct genetic modifications. Nature 1994;368:856–859.
    1. Diebolder CA, et al. Complement is activated by IgG hexamers assembled at the cell surface. Science. 2014;343:1260–1263.
    1. Melis JP, Strumane K, Ruuls SR, Beurskens FJ, Schuurman J, Parren PW. Complement in therapy and disease: regulating the complement system with antibody‐based therapeutics. Mol Immunol 2015;67:117–130.
    1. Di Gaetano N, et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol 2003;171:1581–1587.
    1. Boross P, et al. The in vivo mechanism of action of CD20 monoclonal antibodies depends on local tumor burden. Haematologica 2011;96:1822–1830.
    1. Beum PV, et al. Penetration of antibody‐opsonized cells by the membrane attack complex of complement promotes Ca(2+) influx and induces streamers. Eur J Immunol 2011;41:2436–2446.
    1. Nijhof IS, et al. Upregulation of CD38 expression on multiple myeloma cells by all‐trans retinoic acid improves the efficacy of daratumumab. Leukemia 2015. doi:.
    1. Cartron G, et al. Therapeutic activity of humanized anti‐CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 2002;99:754–758.
    1. Dall'Ozzo S, et al. Rituximab‐dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration‐effect relationship. Cancer Res 2004;64:4664–4669.
    1. van der Veer MS, et al. Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 2011;96:284–290.
    1. Munn DH, McBride M, Cheung NK. Role of low‐affinity Fc receptors in antibody‐dependent tumor cell phagocytosis by human monocyte‐derived macrophages. Cancer Res 1991;51:1117–1123.
    1. Ribatti D, Moschetta M, Vacca A. Macrophages in multiple myeloma. Immunol Lett 2013;161:241–244.
    1. Zheng Y, et al. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug‐induced apoptosis. Blood 2009;114:3625–3628.
    1. Overdijk MB, et al. Antibody‐mediated phagocytosis contributes to the anti‐tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs 2015;7:311–321.
    1. Chaouchi N, Vazquez A, Galanaud P, Leprince C. B cell antigen receptor‐mediated apoptosis. Importance of accessory molecules CD19 and CD22, and of surface IgM cross‐linking. J Immunol 1995;154:3096–3104.
    1. Ghetie MA, Podar EM, Ilgen A, Gordon BE, Uhr JW, Vitetta ES. Homodimerization of tumor‐reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells. Proc Natl Acad Sci USA 1997;94:7509–7514.
    1. Mattes MJ, Michel RB, Goldenberg DM, Sharkey RM. Induction of apoptosis by cross‐linking antibodies bound to human B‐lymphoma cells: expression of Annexin V binding sites on the antibody cap. Cancer Biother Radiopharm 2009;24:185–193.
    1. Shan D, Ledbetter JA, Press OW. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 1998;91:1644–1652.
    1. van der Veer MS, et al. The therapeutic human CD38 antibody daratumumab improves the anti‐myeloma effect of newly emerging multi‐drug therapies. Blood Cancer J 2011;1:e41.
    1. Preyat N, Leo O. Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways. Biochem Pharmacol 2015. doi:.
    1. Horenstein A, et al. NAD+‐metabolizing ectoenzymes in remodeling tumor‐host interactions: the human myeloma model. Cells 2015;4:520.
    1. Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol 2010;10:317–327.
    1. van de Donk NW, et al. Lenalidomide for the treatment of relapsed and refractory multiple myeloma. Cancer Manag Res 2012;4:253–268.
    1. Benboubker L, et al. Lenalidomide and dexamethasone in transplant‐ineligible patients with myeloma. N Engl J Med 2014;371:906–917.
    1. Dimopoulos M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007;357:2123–2132.
    1. Weber DM, et al. Lenalidomide plus dexam‐ethasone for relapsed multiple myeloma in North America. N Engl J Med 2007;357:2133–2142.
    1. Kumar SK, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia 2012;26:149–157.
    1. Nijhof IS, et al. Preclinical evidence for the therapeutic potential of CD38‐targeted immuno‐chemotherapy in multiple myeloma patients refractory to lenalidomide and bortezomib. Clin Cancer Res 2015;21:2802–2810.
    1. Jiang H, et al. SAR650984 (SAR) directly promotes homotypic adhesion‐related multiple myeloma (MM) cell death and SAR‐induced anti‐MM activities are enhanced by pomalidomide, more potently than lenalidomide. Blood 2014;124:2124.
    1. Endell J, Boxhammer R, Wurzenberger C, Ness D, Steidl S. The activity of MOR202, a fully human anti‐CD38 antibody, is complemented by ADCP and is synergistically enhanced by lenalidomide in vitro and in vivo. Blood 2012;120:4018.
    1. Nijhof IS, et al. Daratumumab‐mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti‐KIR antibody IPH2102 and lenalidomide. Haematologica 2015;100:263–268.
    1. Hernandez‐Ilizaliturri FJ, Reddy N, Holkova B, Ottman E, Czuczman MS. Immunomodulatory drug CC‐5013 or CC‐4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res 2005;11:5984–5992.
    1. Quach H, et al. Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 2010;24:22–32.
    1. Miguel JS, et al. Pomalidomide plus low‐dose dexamethasone versus high‐dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM‐003): a randomised, open‐label, phase 3 trial. Lancet Oncol 2013;14:1055–1066.
    1. Leleu X, et al. Pomalidomide plus low‐dose dexamethasone is active and well tolerated in bortezomib and lenalidomide‐refractory multiple myeloma: intergroupe Francophone du Myelome 2009‐02. Blood 2013;121:1968–1975.
    1. Lacy MQ, et al. Pomalidomide plus low‐dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual‐refractory disease. Blood 2011;118:2970–2975.
    1. Jiang H, et al. SAR650984 directly induces multiple myeloma cell death via lysosomal‐associated and apoptotic pathways, which is further enhanced by Pomalidomide. Leukemia 2015. doi:.
    1. Richardson PG, et al. Bortezomib or high‐dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352:2487–2498.
    1. Sonneveld P, et al. Bortezomib‐based versus nonbortezomib‐based induction treatment before autologous stem‐cell transplantation in patients with previously untreated multiple myeloma: a meta‐analysis of phase III randomized, controlled trials. J Clin Oncol 2013;31:3279–3287.
    1. Cai T, Wetzel M, Nicolazzi C, Vallee F, Deckert J. Preclinical characterization of SAR650984, a humanized anti‐CD38 antibody for the treatment of multiple myeloma. Clin Lymph Myeloma Leuk 2013;13:P‐288.
    1. Malavasi F. Editorial: CD38 and retinoids: a step toward a cure. J Leukoc Biol 2011;90:217–219.
    1. Drach J, et al. Retinoic acid‐induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor‐alpha. Cancer Res 1994;54:1746–1752.
    1. San Miguel JF, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008;359:906–917.
    1. Roussel M, et al. Front‐line transplantation program with lenalidomide, bortezomib, and dexamethasone combination as induction and consolidation followed by lenalidomide maintenance in patients with multiple myeloma: a phase II study by the Intergroupe Francophone du Myelome. J Clin Oncol 2014;32:2712–2717.
    1. Lokhorst HM, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 2015;373:1207–1219.
    1. Lonial S, et al. Phase II study of daratumumab (DARA) monotherapy in patients with ≥3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). J Clin Oncol 2015;33:LBA8512.
    1. Plesner T, et al. Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. Blood 2014;124:84.
    1. Mateos M‐V, et al. An open‐label, multicenter, phase 1b study of daratumumab in combination with pomalidomide‐dexamethasone and with backbone regimens in patients with multiple myeloma. EHA Meet 2015;2015:P275.
    1. Martin TG, Hsu K, Strickland SA, Glenn MJ, Mikhael J, Charpentier E. A phase I trial of SAR650984, a CD38 monoclonal antibody, in relapsed or refractory multiple myeloma. J Clin Oncol 2014;32:A8532.
    1. Martin TG, Strickland SA, Glenn M, Zheng W, Daskalakis N, Mikhael JR. SAR650984, a CD38 monoclonal antibody in patients with selected CD38+ hematological malignancies‐ data from a dose‐escalation phase I study. Blood 2013;122:284.
    1. Raab MS, et al. A phase I/IIa study of the human anti‐CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma (rrMM). J Clin Oncol 2015;33:A8574.
    1. Raab M, et al. A phase I/IIa study of the human anti‐CD38 antibody MOR202 (MOR03087) in relapsed or refractory multiple myeloma. Haematologica 2015;100:S789.
    1. Mateos M‐V, et al. A randomized open‐label study of bortezomib, melphalan, and prednisone (VMP) versus daratumumab (DARA) plus VMP in patients with previously untreated multiple myeloma (MM) who are ineligible for high‐dose therapy: 54767414MMY3007 (ALCYONE). J Clin Oncol 2015;33:TPS8608.
    1. Rajkumar SV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538–e548.
    1. Ahn IE, Mailankody S, Korde N, Landgren O. Dilemmas in treating smoldering multiple myeloma. J Clin Oncol 2015;33:115–123.
    1. Dispenzieri A, et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008;111:785–789.
    1. Perez‐Persona E, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 2007;110:2586–2592.
    1. Mateos MV, et al. Lenalidomide plus dexamethasone for high‐risk smoldering multiple myeloma. N Engl J Med 2013;369:438–447.
    1. Korde N, et al. A phase II trial of pan‐KIR2D blockade with IPH2101 in smoldering multiple myeloma. Haematologica 2014;99:e81–e83.
    1. Nijhof I, et al. Expression levels of CD38 and complement inhibitory proteins CD55 and CD59 predict response to daratumumab in multiple myeloma. Haematologica 2015;100:S477.
    1. Marra J, Du J, Hwang J, Wolf JL, Martin TG, Venstrom JM. KIR and HLA genotypes influence clinical outcome in multiple myeloma patients treated with SAR650984 (anti‐CD38) in combination with lenalidomide and dexamethasone. Blood 2014;124:2126.
    1. Schwonzen M, et al. Immunophenotyping of low‐grade B‐cell lymphoma in blood and bone marrow: poor correlation between immunophenotype and cytological/histological classification. Br J Haematol 1993;83:232–239.
    1. Del Poeta G, et al. Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood 2001;98:2633–2639.
    1. Ibrahim S, et al. CD38 expression as an important prognostic factor in B‐cell chronic lymphocytic leukemia. Blood 2001;98:181–186.
    1. Lammerts van Bueren J, et al. Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79. Blood 2014;124:3474.
    1. Matas‐Céspedes A, et al. Daratumumab, a novel human anti‐CD38 monoclonal antibody shows anti‐tumor activity in mouse models of MCL, FL and CLL. Blood 2013;122:378.
    1. Matas‐Céspedes A, et al. Daratumumab, a novel anti‐CD38 monoclonal antibody shows anti‐tumor activity in CLL and hampers leukemia‐microenvironment interactions. Blood 2014;124:4680.
    1. Doshi P, et al. Daratumumab treatment in combination with CHOP or R‐CHOP results in the inhibition or regression of tumors in preclinical models of non‐hodgkins lymphoma. Haematologica 2014;99:P434.
    1. Doshi P, Sasser AK, Axel A, Lammerts van Bueren J. Daratumumab treatment alone or in combination with vincristine results in the inhibition of tumor growth and long term survival in preclinical models of acute lymphocytic leukemia. Haematologica 2014;99:P109.
    1. Dos Santos C, et al. Anti‐leukemic activity of daratumumab in acute myeloid leukemia cells and patient‐derived xenografts. Blood 2014;124:2312.
    1. Groen RW, et al. Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 2012;120:e9–e16.
    1. Dorner T, Radbruch A, Burmester GR. B‐cell‐directed therapies for autoimmune disease. Nat Rev Rheumatol 2009;5:433–441.
    1. Kamal A, Khamashta M. The efficacy of novel B cell biologics as the future of SLE treatment: a review. Autoimmun Rev 2014;13:1094–1101.
    1. Mei HE, Schmidt S, Dorner T. Rationale of anti‐CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 2012;14:S1.
    1. Hiepe F, Dorner T, Hauser AE, Hoyer BF, Mei H, Radbruch A. Long‐lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol 2011;7:170–178.
    1. Mei HE, et al. A unique population of IgG‐expressing plasma cells lacking CD19 is enriched in human bone marrow. Blood 2015;125:1739–1748.
    1. Young D. Effects on Drugs on Clinical Laboratory Tests. 5th edn Washington, DC: AACC Press, 2000.
    1. Chapuy CI, et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015;55:1545–1554.
    1. Oostendorp M, et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion 2015;55:1555–1562.
    1. Berthelier V, Laboureau J, Boulla G, Schuber F, Deterre P. Probing ligand‐induced conformational changes of human CD38. Eur J Biochem 2000;267:3056–3064.
    1. McCudden CR, et al. Interference of monoclonal antibody therapies with serum protein electrophoresis tests. Clin Chem 2010;56:1897–1899.
    1. McCudden C, et al. Assessing clinical response in multiple myeloma (MM) patients treated with monoclonal antibodies (mAbs): validation of a daratumumab IFE reflex assay (DIRA) to distinguish malignant M‐protein from therapeutic antibody. J Clin Oncol 2015;33:8590.
    1. van de Donk NW, Kamps S, Mutis T, Lokhorst HM. Monoclonal antibody‐based therapy as a new treatment strategy in multiple myeloma. Leukemia 2012;26:199–213.
    1. de Tute RM, Shingles J, Rawstron AC, Owen RG. Variable expression of therapeutic antibody targets may have implications for efficacy of therapy in myeloma and waldenstrom macroglobulinaemia. Blood 2014;124:3425.
    1. van Sorge NM, van der Pol WL, van de Winkel JG. FcgammaR polymorphisms: implications for function, disease susceptibility and immunotherapy. Tissue Antigens 2003;61:189–202.
    1. Drent E, et al. CD38 chimeric antigen receptor engineered T cells as therapeutic tools for multiple myeloma. Blood 2014;124:4759.

Source: PubMed

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