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Drugs

, Volume 76, Issue 8, pp 853–867 | Cite as

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

  • Philippe Moreau
  • Niels W. C. J. van de Donk
  • Jesus San Miguel
  • Henk Lokhorst
  • Hareth Nahi
  • Dina Ben-Yehuda
  • Michele Cavo
  • Gordon Cook
  • Michel Delforge
  • Hermann Einsele
  • Sonja Zweegman
  • Heinz Ludwig
  • Christoph Driessen
  • Antonio Palumbo
  • Thierry Facon
  • Torben Plesner
  • Meletios Dimopoulos
  • Pia Sondergeld
  • Pieter Sonneveld
  • María-Victoria Mateos
Therapy in Practice

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.

Keywords

Multiple Myeloma Bortezomib Lenalidomide Overall Response Rate Chimeric Antigen Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

Medical writing and editorial support was provided by Pia Sondergeld (University of Giessen, Germany) and was funded by Janssen.

Conflicts of interest

Philippe Moreau received fees for advisory board participation from Janssen, Celgene, Bristol–Myers Squibb, Novartis, Takeda, and Amgen. Niels W. C. J. van de Donk received a research Grant from Celgene, Janssen Pharmaceuticals, and Amgen. Jesus San Miguel received fees for advisory board participation from Millennium, Celgene, Novartis, Onyx, Janssen, Bristol–Myers Squibb, and Merck Sharp and Dohme. Henk Lokhorst received fees for attending advisory boards on daratumumab (Janssen). Michele Cavo received honoraria from Janssen, Cilag, Takeda, and Bristol–Myers Squibb, and payment for lectures from Janssen, Cilag, and Takeda. Gordon Cook received Grants from Janssen, Celgene, Takeda, and Chugai-Pharmaceutical Co.; consulting fees or honorarium from Janssen, Celgene, Takeda, Sanofi, Bristol–Myers Squibb, Glycomimetics, and Amgen; support for travel from Janssen, Celgene, Takeda, Sanofi; fees for participation in review activities from Celgene, and Glycomimetics; and payment for lectures from Janssen, Celgene, Takeda, Sanofi, Bristol–Myers Squibb, and Amgen. Michel Delforge received a Grant from Celgene (phase IV clinical trial), and honoraria from Amgen, Celgene, Janssen, Novartis, and Takeda. Hermann Einsele received consulting fees or honorarium, payment for lectures, and support for travel from Janssen, Celgene, Amgen, and Novartis. Sonja Zweegman received honoraria for advisory board participation from Celgene, Takeda, Janssen, and Novartis (honorarium for departmental use, not personal use), and lectures for Celgene and Janssen (payment for departmental use only). Heinz Ludwig received fees for participation in data monitoring committees of early daratumumab studies. Christoph Driessen received consulting honorarium related to daratumumab from Janssen–Cilag (not related to the current manuscript). Antonio Palumbo received consulting fees and honoraria from Janssen–Cilag (not related to the current manuscript). Thierry Facon received fees for advisory board participation, as well as support for travel and payment for lectures from Janssen. He undertakes advisory board activities with Janssen and is on the speaker’s bureau for Janssen. Torben Plesner received a research Grant from Janssen, honoraria for advisory board participation from Genmab and Janssen, and payment for lectures from Janssen. Meletios Dimopoulos has received consulting fees or honoraria from Janssen, Celgene, Novartis, and Amgen. Pia Sondergeld received payment from Janssen for the writing of this manuscript. Pieter Sonneveld received Grants from Amgen, Celgene, Janssen, and Karyopharm; consulting fees or honoraria from Amgen, Celgene, Janssen, and Karyopharm; fees for participation in review activities from Celgene and Janssen; provision of writing assistance from Janssen; and payment for lectures from Amgen, Celgene, and Janssen. He has been involved in drug research, i.e. clinical trials, both investigator-initiated and company-initiated, and has served on advisory boards and given lectures in the context of new drug development for multiple myeloma. Maria-Victoria Mateos has received honoraria for lectures and participation in advisory boards from Janssen, Celgene, Takeda, Amgen, and Bristol–Myers Squibb. Hareth Nahi and Dina Ben-Yehuda have no conflicts of interest to declare.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Philippe Moreau
    • 1
  • Niels W. C. J. van de Donk
    • 2
  • Jesus San Miguel
    • 3
  • Henk Lokhorst
    • 2
  • Hareth Nahi
    • 4
  • Dina Ben-Yehuda
    • 5
  • Michele Cavo
    • 6
  • Gordon Cook
    • 7
  • Michel Delforge
    • 8
  • Hermann Einsele
    • 9
  • Sonja Zweegman
    • 2
  • Heinz Ludwig
    • 10
  • Christoph Driessen
    • 11
  • Antonio Palumbo
    • 12
  • Thierry Facon
    • 13
  • Torben Plesner
    • 14
  • Meletios Dimopoulos
    • 15
  • Pia Sondergeld
    • 16
  • Pieter Sonneveld
    • 17
  • María-Victoria Mateos
    • 18
  1. 1.Hematology DepartmentUniversity Hospital Hôtel-DieuNantesFrance
  2. 2.VU University Medical CenterAmsterdamThe Netherlands
  3. 3.University Hospital NavarraPamplonaSpain
  4. 4.Karolinska University Hospital HuddingeStockholmSweden
  5. 5.Hadassah Medical CenterJerusalemIsrael
  6. 6.University School of MedicineBolognaItaly
  7. 7.St James’s University HospitalLeedsUK
  8. 8.Catholic University of LeuvenLeuvenBelgium
  9. 9.Julius Maximilian UniversityWürzburgGermany
  10. 10.Wilhelminen hospitalViennaAustria
  11. 11.Kantonsspital St. GallenSt. GallenSwitzerland
  12. 12.University of TorinoTorinoItaly
  13. 13.University Hospital LilleLilleFrance
  14. 14.Vejle Hospital and University of Southern DenmarkVejleDenmark
  15. 15.University Athens School of MedicineAthensGreece
  16. 16.University of GiessenGiessenGermany
  17. 17.Erasmus MC Cancer InsituteRotterdamThe Netherlands
  18. 18.University Hospital of SalamancaSalamancaSpain

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