Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019, 163(3):279-283

Single agent daratumumab in advanced multiple myeloma possesses significant efficacy even in an unselected "real-world" population

Jiri Minarika, Ludek Pourb, Vladimir Maisnarc, Ivan Spickad, Alexandra Jungovae, Tomas Jelinekf, Lucie Brozovag, Petra Krhovskaa, Vlastimil Scudlaa, Roman Hajekf
a Department of Hemato-oncology, University Hospital Olomouc and Faculty of Medicine, Palacky University Olomouc, Czech Republic
b Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Czech Republic
c Department of Clinical Hematology, University Hospital Hradec Kralove, Czech Republic
d Department of Internal Medicine, University Hospital Praha, Czech Republic
e Department of Haemato-Oncology, University Hospital Pilzen, Czech Republic
f Department of Haematooncology, University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Czech Republic;
g Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University Brno, Czech Republic

Objective: The treatment of relapsed and refractory multiple myeloma (RRMM) remains challenging. The outcomes in highly pretreated populations are unsatisfactory and there is urgent need for novel and safe therapeutic approaches. Recently, daratumumab has been approved for RRMM with promising results even in monotherapy. The aim of this study was to assess the efficacy of single agent daratumumab outside a clinical trial.

Patients and Methods: 14 patients with RRMM and significant pretreatment (median 4.5 previous lines) entered a specific healthcare program and received treatment with single agent daratumumab. They were followed for therapeutic response based on IMWG criteria, and incidence of adverse events. The data were collected using the Registry of Monoclonal Gammopathies.

Results: The overall response rate was 38.5%. 23.1% of patients reached very good partial response, 15.4% reached partial remission, 15.4% had minimal response, 38.5% had stable disease and 7.7% had progressive disease. The median progression free survival was 4.6 months and median overall survival was not achieved. The toxicities were mostly mild, only infectious complications and hematological toxicity reached grade III.

Conclusion: We conclude that daratumumab has significant activity in highly pretreated RRMM even as a single agent, with an acceptable toxicity profile and survival impact.

Keywords: multiple myeloma, relapsed and refractory, daratumumab, progression free survival, overall survival

Received: May 15, 2018; Revised: July 25, 2018; Accepted: October 12, 2018; Prepublished online: November 6, 2018; Published: September 23, 2019  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Minarik, J., Pour, L., Maisnar, V., Spicka, I., Jungova, A., Jelinek, T., ... Hajek, R. (2019). Single agent daratumumab in advanced multiple myeloma possesses significant efficacy even in an unselected "real-world" population. Biomedical papers, 163(3), 279-283
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Krejcik J, Casneuf T, Nijhof IS, Verbist B, Bald J, Plesner T, Syed K, Liu K, van de Donk NWCJ, Weiss BM, Ahmadi T, Lokhorst HM, Mutis T, Sasser AK. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood 2016;128:384-94. Go to original source... Go to PubMed...
    2. Jelinek T, Hajek R. Monoclonal antibodies - A new era in the treatment of multiple myeloma. Blood Rev 2016;30:101-10. Go to original source... Go to PubMed...
    3. de Weers M, Tai Y-T, van der Veer MS, Bakker JM, Vink T, Jacobs DC, Oomen LA, Peipp M, Valerius T, Slootstra JW, Mutis T, Bleeker WK, Anderson KC, Lokhorst HM, van de Winkel JG, Parren PW. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. J Immunol 2011;186:1840-8. Go to original source... Go to PubMed...
    4. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Blade J, Scott EC, Oriol A, Bardeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016;387:1551-60. Go to original source... Go to PubMed...
    5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/761036Orig1s000lbledt.pdf Accessed Feb 14, 2018.
    6. Radocha J, Pour L, Spicka I, Scudla V, Gregora E, Frankova H, Hajek R, Schutzova M, Sykora P, Kessler P, Adamova D, Wrobel M, Sedlarikova L, Sevcikova S, Horinek D, Pelcova J, Brozova L, Jarkovsky J, Maisnar V. Registry of Monoclonal Gammopathies (RMG) in the Czech Republic. Blood 2015;126:4514. Go to original source...
    7. Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson KC. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood 2014;123:1826-32. Go to original source... Go to PubMed...
    8. Hajek R, Masszi T, Petrucci MT, Palumbo A, Rosinol L, Nagler A, Yong KL, Oriol A, Minarik J, Pour L, Dimopoulos MA, Maisnar V, Rossi D, Kasparu H, van Droogenbroeck J, Yehude DB, Hardan I, Jenner M, Calbecka M, David M, de la Rubia J, Drach J, Gasztonyi Z, Gornik S, Leleu X, Munder M, Offidani M, Zojer N, Rajangam K, Chang YL, San Miguel JF, Ludwig H. A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). Leukemia 2017;31:107-14. Go to original source... Go to PubMed...
    9. Usmani SZ, Diels J, Ito T, Mehra M, Khan I, Lam A. Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. Am J Hematol 2017;92:E146-E152. Go to original source... Go to PubMed...
    10. Jelinek T, Maisnar V, Pour L, Spicka I, Minarik J, Gregora E, Kessler P, Sykora M, Frankova H, Adamova D, Wrobel M, Mikula P, Jarkovsky J, Diels J, Gatopoulou X, Vesela S, Besson H, Brozova L, Ito T, Hajek R. Adjusted comparison of daratumumab monotherapy versus real-world historical control data from the Czech Republic in heavily pretreated and highly refractory multiple myeloma patients. Curr Med Res Opin 2018;34(5):775-83. doi: 10.1080/03007995.2017.1410121 Go to original source... Go to PubMed...
    11. Blair HA. Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Drugs 2017;18:2013-24. Go to original source... Go to PubMed...
    12. Lentzsch S, Weisel KC, Mateos M-V, Hungria V, Munder M, Nooka A, Mark T, Quach H, Scott E, Lee J, Sonneveld P, Casneuf T, Chiu C, Qin X, Amin H, Thiyagarajah P, Schecter J, Qi M, Spencer A. Daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (RRMM): Efficacy and safety update (CASTOR). J Clin Oncol 2017;35(S15):8036. doi: 10.1200/JCO.2017.35.15_suppl.8036 Go to original source...
    13. Dimopoulos MA, White DJ, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Trivedi S, Wu K, Casneuf T, Chiu C, Schecter J, Moreau P. Daratumumab, Lenalidomide, and Dexamethasone (DRd) Versus Lenalidomide and Dexamethasone (Rd) in Relapsed or Refractory Multiple Myeloma (RRMM): Updated Efficacy and Safety Analysis of Pollux. Blood 2017;130(S1):739. Go to original source...
    14. Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med,2016;375:754-66. Go to original source... Go to PubMed...
    15. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon S-S, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O“Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2016;375:1319-31. Go to original source... Go to PubMed...
    16. Mateos MV, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Kaplan P, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova A, Yoon S-S, Iosava G, Fujisaki T, Garg M, Chiu C, Wang J, Carson R, Crist W, Deraedt W, Nguyen H, Qi M, San Miguel J. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med 2018;378:518-28. Go to original source... Go to PubMed...
    17. Hofmeister C, Chari A, Cohen YC, Spencer A, Voorhees PM, estell J, Venner CP, Sandhu I, Jenner MW, Williams C, Cavo M, van de Donk NWCJ, Beksac M, Kuppens S, Bandekar R, Neff T, Heuck C, Qi M, Goldschmidt H, Landgren O. Daratumumab monotherapy for patients with intermediate or high-risk smoldering multiple myeloma (SMM): CENTAURUS, a randomized, open-label, multicenter phase 2 study. Blood 2017;35(S1):510.
    18. Minarik J, Novak M, Flodr P, Balcarkova J, Mlynarcikova M, Krhovska P, Pika T, Pikalova Z, Bacovsky J, Scudla V. CD38 negative relapse in multiple myeloma after daratumumab based chemotherapy. Eur J Haematol 2017;99:186-9. Go to original source... Go to PubMed...

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits use, distribution, and reproduction in any medium, provided the original publication is properly cited. No use, distribution or reproduction is permitted which does not comply with these terms.


    Return to the content