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CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(01): 57-60
DOI: 10.4103/ijmpo.ijmpo_263_19
Drug Review

Daratumumab

Vishnu Gopal
Department of Medical Oncology, JIPMER, Puducherry, India
,
Biswajit Dubashi
Department of Medical Oncology, JIPMER, Puducherry, India
› Author Affiliations Financial support and sponsorship Nil.
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Abstract

Multiple myeloma is a proliferative disorder of plasma cells in the bone marrow with excessive monoclonal protein production. Despite the evolution of multiple drugs and management strategies including maintenance and autologous stem cell transplantation, the long-term results still remain undesirable. Those patients with double refractoriness to immunomodulatory drugs and proteosome inhibitors have dismal prognosis and rarely get back into durable remission. The identification of CD38 as a therapeutic target for multiple myeloma resulted in the clinical development of anti-CD38 antibodies. Daratumumab is an IgG1 human monoclonal antibody that binds to the CD38 protein. The implementation of daratumumab in clinical practice is widely considered as a significant milestone in the management of multiple myeloma. The salient pharmacological aspects and clinical evolution of the drug are briefly discussed in this review.

Keywords

CD38 - daratumumab - multiple myeloma


Publication History

Received: 23 December 2019

Accepted: 10 February 2020

Article published online:
23 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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  • References

  • 1 Bora K. Distribution of multiple myeloma in India: Heterogeneity in incidence across age, sex and geography. Cancer Epidemiol 2019; 59: 215-20
    CrossrefPubMedGoogle Scholar
  • 2 Overdijk MB, Verploegen S, Bögels M, van Egmond M, Lammerts van Bueren JJ, Mutis T. et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs 2015; 7: 311-21
    CrossrefPubMedGoogle Scholar
  • 3 Sanchez L, Wang Y, Siegel DS, Wang ML. Daratumumab: A first-in-class CD38 monoclonal antibody for the treatment of multiple myeloma. J Hematol Oncol 2016; 9: 51
    CrossrefPubMedGoogle Scholar
  • 4 Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T. et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood 2016; 128: 384-94
    CrossrefPubMedGoogle Scholar
  • 5 Clemens PL, Yan X, Lokhorst HM, Lonial S, Losic N, Khan I. et al. Pharmacokinetics of daratumumab following intravenous infusion in relapsed or refractory multiple myeloma after prior proteasome inhibitor and immunomodulatory drug treatment. Clin Pharmacokinet 2017; 56: 915-24
    CrossrefPubMedGoogle Scholar
  • 6 Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M. et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 2015; 373: 1207-19
    CrossrefPubMedGoogle Scholar
  • 7 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. Ther Adv Hematol 2015; 6: 120-7
    CrossrefPubMedGoogle Scholar
  • 8 Khagi Y, Mark TM. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther 2014; 7: 1095-100
    PubMedGoogle Scholar
  • 9 Cavo M, Dimopoulos MA, San-Miguel J, Jakubowiak AJ, Suzuki K, Yoon SS. et al. Impact of baseline renal function on efficacy and safety of daratumumab plus bortezomib-melphalan-prednisone (VMP) in patients (Pts) with newly diagnosed multiple myeloma (NDMM) ineligible for transplantation (ALCYONE). J Clin Oncol 2018; 36 (Suppl. 15) e20024
    CrossrefGoogle Scholar
  • 10 Raedler LA. Darzalex (daratumumab):First anti-CD38 monoclonal antibody approved for patients with relapsed multiple myeloma. Am Health Drug Benefits 2016; 9: 70-3
    PubMedGoogle Scholar
  • 11 Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ. et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial. Lancet 2016; 387: 1551-60
    CrossrefPubMedGoogle Scholar
  • 12 Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ. et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375: 1319-31
    CrossrefPubMedGoogle Scholar
  • 13 Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M. et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375: 754-66
    CrossrefPubMedGoogle Scholar
  • 14 Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ. et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017; 130: 974-81
    CrossrefPubMedGoogle Scholar
  • 15 Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S. et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med 2018; 378: 518-28
    CrossrefPubMedGoogle Scholar
  • 16 Facon T, Kumar S, Plesner T, Orlowski RZ, Moreau P, Bahlis N. et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med 2019; 380: 2104-15
    CrossrefPubMedGoogle Scholar
  • 17 Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L. et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): A randomised, open-label, phase 3 study. Lancet 2019; 394: 29-38
    CrossrefPubMedGoogle Scholar
  • 18 Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S. et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 2016; 128: 37-44
    CrossrefPubMedGoogle Scholar
  • 19 Sullivan HC, Gerner-Smidt C, Nooka AK, Arthur CM, Thompson L, Mener A. et al. Daratumumab (anti-CD38) induces loss of CD38 on red blood cells. Blood 2017; 129: 3033-7
    CrossrefPubMedGoogle Scholar
  • 20 Oostendorp M, Lammerts van Bueren JJ, Doshi P, Khan I, Ahmadi T, Parren PW. et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion 2015; 55: 1555-62
    CrossrefPubMedGoogle Scholar
  • 21 Chapuy CI, Nicholson RT, Aguad MD, Chapuy B, Laubach JP, Richardson PG. et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015; 55: 1545-54
    CrossrefPubMedGoogle Scholar
  • 22 Nooka AK, Kaufman JL, Hofmeister CC, Joseph NS, Heffner TL, Gupta VA. et al. Daratumumab in multiple myeloma. Cancer 2019; 125: 2364-82
    CrossrefPubMedGoogle Scholar
  • 23 Rosenberg AS, Bainbridge S, Pahwa R, Jialal I. Investigation into the interference of the monoclonal antibody daratumumab on the free light chain assay. Clin Biochem 2016; 49: 1202-4
    CrossrefPubMedGoogle Scholar
  • 24 McCudden C, Axel AE, Slaets D, Dejoie T, Clemens PL, Frans S. et al. Monitoring multiple myeloma patients treated with daratumumab: Teasing out monoclonal antibody interference. Clin Chem Lab Med 2016; 54: 1095-104
    CrossrefPubMedGoogle Scholar