Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma

Citation:

Moreau P, Van De Donk NWCJ, Miguel JS, Lokhorst H, Nahi H, Ben-Yehuda D, Cavo M, Cook G, Delforge M, Einsele H, et al. Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma. Drugs [Internet]. 2016;76(8):853 - 867.

Abstract:

Monoclonal antibodies (mAbs) are a recent addition to multiple myeloma (MM) therapies and a number of mAbs directed at myeloma cell surface molecules are in development. Daratumumab is a CD38 mAb that has demonstrated substantial activity and good tolerability in four phase I, phase I/II and phase II studies as monotherapy, as well as in combination with current standard treatments in MM. The positive results obtained in the relapsed/refractory setting in patients with advanced-stage disease and in a small number of patients with newly diagnosed disease provide the rationale for the investigation of the agent in a number of ongoing phase III trials. mAbs are generally better tolerated than conventional chemotherapy; however, their use requires other special considerations. Such factors include those common to all mAbs, namely infusion-related reactions, but also factors that are observed with mAbs used in myeloma, such as interference with response assessment, or factors that are related to CD38 mAbs such as daratumumab, for instance blood typing interference. Our review provides an overview of the results from the daratumumab clinical trials conducted to date, as well as practical management considerations for the use of daratumumab based on our experience with the agent. © 2016 Springer International Publishing Switzerland.

Notes:

Cited By :1Export Date: 18 February 2017References: Grillo-López, A.J., White, C.A., Dallaire, B.K., Rituximab: The first monoclonal antibody approved for the treatment of lymphoma (2000) Curr Pharm Biotechnol, 1 (1), pp. 1-9. , 11467356;Sehn, L.H., Donaldson, J., Chhanabhai, M., Fitzgerald, C., Gill, K., Klasa, R., Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia (2005) J Clin Oncol, 23 (22), pp. 5027-5033. , 1:CAS:528:DC%2BD2MXpsFWmtLs%3D 15955905; Majithia, N., Rajkumar, S.V., Lacy, M.Q., Buadi, F.K., Dispenzieri, A., Gertz, M.A., Outcomes of primary refractory multiple myeloma and the impact of novel therapies (2015) Am J Hematol, 90 (11), pp. 981-985. , 1:CAS:528:DC%2BC2MXhslegur3I 26214732; Kumar, S.K., Lee, J.H., Lahuerta, J.J., Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: A multicenter International Myeloma Working Group study (2012) Leukemia, 26, pp. 149-157. , 1:CAS:528:DC%2BC38XntF2ksQ%3D%3D 21799510 4109061; Laubach, J.P., Tai, Y.T., Richardson, P.G., Anderson, K.C., Daratumumab granted breakthrough drug status (2014) Expert Opin Investig Drugs, 23 (4), pp. 445-452. , 1:CAS:528:DC%2BC2cXktFegurY%3D 24555809; FDA Approves Darzalex for Patients with Previously Treated Multiple Myeloma, , http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm, US FDA Accessed 25 Mar 2016; Janssen Submits Marketing Authorisation Application for Daratumumab for European Patients with Heavily Pre-treated Multiple Myeloma, , http://www.myelomabeacon.com/pr/2015/09/09/daratumumab-european-marketin..., The Myeloma Beacon™ Accessed 25 Mar 2016; Mehta, K., Shahid, U., Malavasi, F., HumanCD38, a cell-surface protein with multiple functions (1996) FASEB J., 10 (12), pp. 1408-1417. , 1:CAS:528:DyaK28XmsVSgu7o%3D 8903511; Funaro, A., Malavasi, F., Human CD38, a surface receptor, an enzyme, an adhesion molecule and not a simple marker (1999) J Biol Regul Homeost Agents, 13 (1), pp. 54-61. , 1:CAS:528:DyaK1MXotFWrtLs%3D 10432444; Malavasi, F., Deaglio, S., Funaro, A., Ferrero, E., Horenstein, A.L., Ortolan, E., Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology (2008) Physiol Rev, 88 (3), pp. 841-886. , 1:CAS:528:DC%2BD1cXpslKgs7s%3D 18626062; Deaglio, S., Mehta, K., Malavasi, F., Human CD38: A (r)evolutionary story of enzymes and receptors (2001) Leuk Res, 25 (1), pp. 1-12. , 1:CAS:528:DC%2BD3MXht12jurk%3D 11137554; Quarona, V., Ferri, V., Chillemi, A., Bolzoni, M., Mancini, C., Zaccarello, G., Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche (2015) Ann N y Acad Sci, 1335, pp. 10-22. , 1:CAS:528:DC%2BC2MXps1OqsL4%3D 25048519; Deaglio, S., Vaisitti, T., Aydin, S., Ferrero, E., Malavasi, F., In-tandem insight from basic science combined with clinical research: CD38 as both marker and key component of the pathogenetic network underlying chronic lymphocytic leukemia (2006) Blood, 108 (4), pp. 1135-1144. , 1:CAS:528:DC%2BD28Xot1ymtL4%3D 16621959; Partida-Sánchez, S., Cockayne, D.A., Monard, S., Jacobson, E.L., Oppenheimer, N., Garvy, B., Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo (2001) Nat Med, 7 (11), pp. 1209-1216. , 11689885; Partida-Sánchez, S., Randall, T.D., Lund, F.E., Innate immunity is regulated by CD38, an ecto-enzyme with ADP-ribosyl cyclaseactivity (2003) Microbes Infect, 5 (1), pp. 49-58. , 12593973; Fedele, G., Di Girolamo, M., Recine, U., Palazzo, R., Urbani, F., Horenstein, A.L., CD38 ligation in peripheral blood mononuclear cells of myeloma patients induces release of protumorigenic IL-6 and impaired secretion of IFNγ cytokines and proliferation (2013) Mediat Inflamm, 2013, p. 564687; Terstappen, L.W., Huang, S., Safford, M., Lansdorp, P.M., Loken, M.R., Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34 + CD38-progenitor cells (1991) Blood, 77 (6), pp. 1218-1227. , 1:STN:280:DyaK3M7lvFKhtw%3D%3D 1705833; Theilgaard-Mönch, K., Raaschou-Jensen, K., Schjødt, K., Heilmann, C., Vindeløv, L., Jacobsen, N., Pluripotent and myeloid-committed CD34+ subsets in hematopoietic stem cell allografts (2003) Bone Marrow Transpl, 32 (12), pp. 1125-1133; Lin, P., Owens, R., Tricot, G., Wilson, C.S., Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma (2004) Am J Clin Pathol, 121 (4), pp. 482-488. , 15080299; Santonocito, A.M., Consoli, U., Bagnato, S., Milone, G., Palumbo, G.A., Di Raimondo, F., Flow cytometric detection of aneuploidCD38(++) plasmacells and CD19(+) B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients (2004) Leuk Res, 28 (5), pp. 469-477. , 15068900; Chillemi, A., Zaccarello, G., Quarona, V., Ferracin, M., Ghimenti, C., Massaia, M., Anti-CD38 antibody therapy: Windows of opportunity yielded by the functional characteristics of the target molecule (2013) Mol Med, 19, pp. 99-108. , 1:CAS:528:DC%2BC3sXhtVGjtbvE 23615966 3667209; De Weers, M., Tai, Y.T., Van Der Veer, M.S., Bakker, J.M., Vink, T., Jacobs, D.C., Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors (2011) J Immunol., 186 (3), pp. 1840-1848. , 21187443; Overdijk, M.B., Verploegen, S., Bögels, M., Van Egmond, M., Lammerts Van Bueren, J.J., Mutis, T., Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiplemyeloma (2015) MAbs., 7 (2), pp. 311-321. , 1:CAS:528:DC%2BC28XksVSqtL8%3D 25760767 4622648; Jansen, J.H., Boross, P., Overdijk, M.B., Van Bueren, J.J., Parren, P.W., Leusen, J.H., Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking [abstract no. 2974]. American Society of Hematology Proceedings 2012 (2012) Blood, 120 (21), p. 2974; Lammerts Van Bueren, J., Jakobs, D., Kaldenhoven, N., Roza, M., Hiddingh, S., Meesters, J., Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79 [abstract no. 3474] (2014) Blood, 124 (21), p. 3474; Phipps, C., Chen, Y., Gopalakrishnan, S., Tan, D., Daratumumab and its potential in the treatment of multiple myeloma: Overview of the preclinical and clinical development (2015) Ther Adv Hematol., 6 (3), pp. 120-127. , 1:CAS:528:DC%2BC2MXhslGhtr%2FN 26137203 4480519; Krejcik, J., Casneuf, T., Nijhof, I., Verbist, B., Bald, J., Plesner, T., Immunomodulatory effects and adaptive immune response to daratumumab in multiple myeloma [abstract no. 3037] (2015) American Society of Hematology 57th Annual Meeting and Exposition, , 5-8 Dec Orlando (FL); Van Der Veer, M.S., De Weers, M., Van Kessel, B., Bakker, J.M., Wittebol, S., Parren, P.W., Towards effective immunotherapy of myeloma: Enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab (2011) Haematologica, 96 (2), pp. 284-290. , 21109694 3031697; Van Der Veer, M.S., De Weers, M., Van Kessel, B., Bakker, J.M., Wittebol, S., Parren, P.W., The therapeutic human CD38 antibody daratumumab improves the anti-myeloma effect of newly emerging multi-drug therapies (2011) Blood Cancer J., 1 (10), p. e41. , 22829073 3255255; Nijhof, I.S., Groen, R.W., Noort, W.A., Van Kessel, B., De Jong-Korlaar, R.A., Bakker, J.M., Preclinical evidence for the therapeutic potential of CD38-targeted immuno-chemotherapy in multiple myeloma patients refractory to lenalidomide and bortezomib (2015) Clin Cancer Res, 21 (12), pp. 2802-2810. , 1:CAS:528:DC%2BC2MXhtVaju77K 25398450; Lokhorst, H.M., Plesner, T., Laubach, J.P., Nahi, H., Gimsing, P., Hansson, M., Targeting CD38 with daratumumab monotherapy in multiple myeloma (2015) N Engl J Med, 373 (13), pp. 1207-1219. , 1:CAS:528:DC%2BC28XkslKrtQ%3D%3D 26308596; Lonial, S., Weiss, B.M., Usmani, S.Z., Singhal, S., Chari, A., Bahlis, N.J., Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial (2016) Lancet. Epub; Usmani, S., Weiss, B., Bahlis, N.J., Belch, A., Lonial, S., Lokhorst, H., Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma [abstract no. 29] (2015) American Society of Hematology 57th Annual Meeting and Exposition, , 5-8 Dec Orlando (FL); Usmani, S., Ahmadi, T., Ng, Y., Lam, A., Potluri, R., Mehra, M., Analyses of real world data on overall survival in multiple myeloma patients with at least 3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and an IMiD [abstract no. 4498] (2015) American Society of Hematology 57th Annual Meeting and Exposition, , 5-8 Dec Orlando (FL); Plesner, T., Arkenau, H.T., Lokhorst, H.M., Gimsing, P., Krejcik, J., Lemech, C., Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma [abstract no. 84] (2014) Blood, 124 (21), p. 84; Plesner, T., Arkenau, H.T., Gimsing, P., Krejcik, J., Lemech, C., Minnema, M.C., Aratumumab in combination with lenalidomide and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: Updated results of a phase 1/2 study (GEN503) [abstract no. 507] (2015) Blood, 126 (23), p. 507; Mateos, M., An open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide-dexamethasone and with backbone regimens in patients with multiple myeloma [abstract no. P275] (2015) European Hematology Association 20th Congress, , 11-14 Jun, Vienna; Moreau P, M., An open-label, multicenter, phase 1b study of daratumumab in combination with backbone regimens in patients with multiple myeloma [abstract no. 176] (2014) American Society of Hematology 56th Annual Meeting and Exposition, , 6-9 Dec, San Francisco (CA); Chari, A., Lonial, S., Suvannasankha, A., Fay, J.W., Arnulf, B., Ifthikharuddin, J.J., Open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma [abstract no. 508] (2015) American Society of Hematology 57th Annual Meeting and Exposition, , 5-8 Dec, Orlando (FL); Darzalex™ (Daratumumab) Injection for Intravenous Infusion 100 mg/5 ML, 400 mg/20 ML, , https://www.darzalex.com, Accessed 25 Mar 2016; Kroll, M.H., Elin, R.J., Interference with clinical laboratory analyses (1994) Clin Chem, 40 (11), pp. 1996-2005. , 1:CAS:528:DyaK2cXmvFKhsb4%3D 7955368; King, R.I., Florkowski, C.M., How paraproteins can affect laboratory assays: Spurious results and biological effects (2010) Pathology., 42 (5), pp. 397-401. , 1:CAS:528:DC%2BC3cXovVCrsrc%3D 20632813; Oostendorp, M., Lammerts Van Bueren, J.J., Doshi, P., Khan, I., Ahmadi, T., Parren, P.W., When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy (2015) Transfusion., 55 (6), pp. 1555-1562. , 25988285; Ostrov, B.E., Amsterdam, D., The interference of monoclonal antibodies with laboratory diagnosis: Clinical and diagnostic implications (2013) Immunol Invest, 42 (8), pp. 673-690. , 1:CAS:528:DC%2BC3sXhsFynsbrO 24094033; Chapuy, C.I., Nicholson, R.T., Aguad, M.D., Chapuy, B., Laubach, J.P., Richardson, P.G., Resolving the daratumumab interference with blood compatibility testing (2015) Transfusion., 55 (6), pp. 1545-1554. , 1:CAS:528:DC%2BC2MXhtVOnt73E 25764134; Zocchi, E., Franco, L., Guida, L., Benatti, U., Bargellesi, A., Malavasi, F., A single protein immunologically identified as CD38 displays NAD1 glycohydrolase, ADP-ribosylcyclase and cyclic ADP-ribosehydrolase activities at the outer surface of human erythrocytes (1993) Biochem Biophys Res Commun., 196, pp. 1459-1465. , 1:CAS:528:DyaK2cXkvVKiuw%3D%3D 8250903; Albeniz, I., Demir, O., Türker-Sener, L., Yalçintepe, L., Nurten, R., Bermek, E., Erythrocyte CD38 as a prognostic marker in cancer (2007) Hematology., 12 (5), pp. 409-414. , 1:CAS:528:DC%2BD2sXhtVOitLvM 17852458; Chari, A., Satta, T., Tayal, A., Jagannath, S., Cho, H.J., Parekh, S., Outcomes and management of red blood cell transfusions in multiple myeloma patients treated with daratumumab [abstract no. 3571] (2015) American Society of Hematology 57th Annual Meeting and Exposition, , 5-8 Dec, Orlando (FL); Bossuyt, X., Interferences in clinical capillary zone electrophoresis of serum proteins (2004) Electrophoresis, 25, pp. 1485-1487. , 1:CAS:528:DC%2BD2cXlt1Oiu7g%3D 15188230; McCudden, C.R., Voorhees, P.M., Hainsworth, S.A., Whinna, H.C., Chapman, J.F., Hammett-Stabler, C.A., Interference of monoclonal antibody therapies with serum protein electrophoresis tests (2010) Clin Chem, 56 (12), pp. 1897-1899. , 1:CAS:528:DC%2BC3cXhsF2js7zF 20940329; Genzen, J.R., Kawaguchi, K.R., Furman, R.R., Detection of a monoclonal antibody therapy (ofatumumab) by serum protein and immunofixation electrophoresis (2011) Br J Haematol, 155 (1), pp. 123-125. , 1:CAS:528:DC%2BC3MXhtlCgsL3P 21521182; Axel, A.E., McCudden, C.R., Xie, H., Hall, B.M., Sasser, A.K., Development of clinical assay to mitigate daratumumab, an IgG1κ monoclonal antibody, interference with serum immunofixation (IFE) and clinical assessment of M-protein response in multiple myeloma [abstract no. 2563] (2014) Proceedings of the American Association for Cancer Research (AACR) Annual Meeting 2014, , 5-9 April, San Diego (CA); Lonial, S., Dimopoulos, M., Palumbo, A., White, D., Grosicki, S., Spicka, I., ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma (2015) N Engl J Med, 373 (7), pp. 621-631. , 1:CAS:528:DC%2BC2MXhsFaisLvL 26035255; McCudden, C., Axel, A., Slaets, D., Frans, S., Bald, J., Schecter, J.M., 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 [abstract no. 8590] (2015) J Clin Oncol, 33, p. 8590; Durie, B.G.M., San Miguel, J.F., Blade, J., Rajkumar, S.V., Clarification of the definition of complete response in multiple myeloma (2015) Leukemia, 29 (12), pp. 2416-2417. , on behalf of the International Myeloma Working Group 1:CAS:528:DC%2BC2MXhvVyktbbF 26487274; Zanotti, K.M., Markman, M., Prevention and management of antineoplastic-induced hypersensitivity reactions (2001) Drug Saf, 24, pp. 767-779. , 1:CAS:528:DC%2BD3MXntlansLw%3D 11676304; Lenz, H.J., Management and preparedness for infusion and hypersensitivity reactions (2007) Oncologist., 12 (5), pp. 601-609. , 1:CAS:528:DC%2BD2sXntVynsL8%3D 17522249; Cornwell, G.G., 3rd, Pajak, T.F., McIntyre, O.R., Hypersensitivity reactions to ivmelphalan during treatment of multiple myeloma: Cancer and Leukemia Group B experience (1979) Cancer Treat Rep, 63 (3), pp. 399-403. , 427822; Chanan-Khan, A., Szebeni, J., Savay, S., Liebes, L., Rafique, N.M., Alving, C.R., Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): Possible role in hypersensitivity reactions (2003) Ann Oncol, 14 (9), pp. 1430-1437. , 1:STN:280:DC%2BD3svhsFSjtQ%3D%3D 12954584; Chung, C.H., Managing premedications and the risk for reactions to infusional monoclonal antibody therapy (2008) Oncologist., 13 (6), pp. 725-732. , 1:CAS:528:DC%2BD1cXpt1CktbY%3D 18586928; Siegel, D.S., From clinical trials to clinical practice: Single-agent carfilzomib adverse events and their management in patients with relapsed and/or refractory multiple myeloma (2013) Ther Adv Hematol., 4 (6), pp. 354-365. , 1:CAS:528:DC%2BC2cXjvFOqur4%3D 24319571 3854560; Guan, M., Zhou, Y.P., Sun, J.L., Chen, S.C., Adverse events of monoclonal antibodies used for cancer therapy (2015) Biomed Res Int., 2015, p. 428169. , 26075239 4436450; Meisel, K., Rizvi, S., Complications of monoclonal antibody therapy (2011) Med Health R I., 94 (11), pp. 317-319. , 22204093; Voorhees, P., Weiss, B., Usmani, S., Huaibao, F., Uhlar, C.M., Khan, I., Management of infusion-related reactions following daratumumab monotherapy in patients with ≥3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (SIRIUS) [abstract no. 1829] (2015) Blood, 126 (23), p. 1829; Blimark, C., Holmberg, E., Mellqvist, U.H., Landgren, O., Björkholm, M., Hultcrantz, M., Multiple myeloma and infections: A population-based study on 9253 multiple myeloma patients (2015) Haematologica, 100 (1), pp. 107-113. , 25344526 4281323; Alici, E., Chrobok, M., Lund, J., Ahmadi, T., Khan, I., Duru, A.D., Re-challenging with anti-CD38 monotherapy in triple-refractory multiple myeloma patients is a feasible and safe approach (2015) Br J Haematol. Epub;

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