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Daratumumab in multiple myeloma: experience of the multiple myeloma GIMEMA Lazio group

Annals of Hematology volume 100, pages 1059–1063 (2021)Cite this article

Abstract

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

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References

  1. de Weers M, Tai YT, 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 (2011) Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 186:1840–1848

    Article  Google Scholar 

  2. Overdijk MB, Verploegen S, Bogels M et al (2015) Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 7:311–321

    CAS  Article  Google Scholar 

  3. 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, Le Blanc 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 (2016) Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 387:1551–1560

    CAS  Article  Google Scholar 

  4. Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, Minnema MC, Lassen U, Krejcik J, Palumbo A, van de Donk NWCJ, Ahmadi T, Khan I, Uhlar CM, Wang J, Sasser AK, Losic N, Lisby S, Basse L, Brun N, Richardson PG (2015) Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 373:1207–1219

    CAS  Article  Google Scholar 

  5. Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, Sasser AK, Axel A, Feng H, Uhlar CM, Wang J, Khan I, Ahmadi T, Nahi H (2016) Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 128:37–44

    CAS  Article  Google Scholar 

  6. Usmani SZ, Diels J, Ito T, Mehra M, Khan I, Lam A (2017) Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: an adjusted treatment comparison. Am J Hematol 92:E146–E152

    CAS  Article  Google Scholar 

  7. Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, Haessler J, Feather J, Hoering A, Moreau P, LeLeu X, Hulin C, Klein SK, Sonneveld P, Siegel D, Blade J, Goldschmidt H, Jagannath S, Miguel JS, Orlowski R, Palumbo A, Sezer O, Rajkumar SV, Durie BG, International Myeloma WorkingGroup (2012) Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia 26:149–157

    CAS  Article  Google Scholar 

  8. 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, CASTOR investigators (2016) Daratumumab, Bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 375(8):754–766

    CAS  Article  Google Scholar 

  9. Spencer A, Lentzsch S, Weisel K, Avet-Loiseau H, Mark TM, Spicka I, Masszi T, Lauri B, Levin MD, Bosi A, Hungria V, Cavo M, Lee JJ, Nooka AK, Quach H, Lee C, Barreto W, Corradini P, Min CK, Scott EC, Chanan-Khan AA, Horvath N, Capra M, Beksac M, Ovilla R, Jo JC, Shin HJ, Sonneveld P, Soong D, Casneuf T, Chiu C, Amin H, Qi M, Thiyagarajah P, Sasser AK, Schecter JM, Mateos MV (2018) Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica 103(12):2079–2087

    CAS  Article  Google Scholar 

  10. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, 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, POLLUX investigators (2016) Daratumumab, Lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 375(14):1319–1331

    CAS  Article  Google Scholar 

  11. Dimopoulos MA, San-Miguel J, Belch A, White D, Benboubker L, Cook G, Leiba M, Morton J, Ho PJ, Kim K, Takezako N, Moreau P, Kaufman JL, Sutherland HJ, Lalancette M, Magen H, Iida S, Kim JS, Prince HM, Cochrane T, Oriol A, Bahlis NJ, Chari A, O'Rourke L, Wu K, Schecter JM, Casneuf T, Chiu C, Soong D, Sasser AK, Khokhar NZ, Avet-Loiseau H, Usmani SZ (2018) Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica 103(12):2088–2096. https://doi.org/10.3324/haematol.2018.194282Epub 2018 Sep 20

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 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 (2016) Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood 128:384–394

    CAS  Article  Google Scholar 

  13. Chatterjee S, Daenthanasanmak A, Chakraborty P, Wyatt MW, Dhar P, Selvam SP, Fu J, Zhang J, Nguyen H, Kang I, Toth K, Al-Homrani M, Husain M, Beeson G, Ball L, Helke K, Husain S, Garrett-Mayer E, Hardiman G, Mehrotra M (2018) CD38-NAD+Axis regulates immunotherapeutic anti-tumor T cell response. Cell Metab 27:85–100.e8

    CAS  Article  Google Scholar 

  14. Marlein CR, Piddock RE, Mistry JJ, Zaitseva L, Hellmich C, Horton RH, Zhou Z, Auger MJ, Bowles KM, Rushworth SA (2019 May 1) CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma. Cancer Res 79(9):2285–2297

    CAS  Article  Google Scholar 

  15. Nooka AK, Kastritis E, Dimopoulos MA, Lonial S (2015) Treatment options for relapsed and refractory multiple myeloma. Blood 125:3085–3099

    CAS  Article  Google Scholar 

  16. Boyle EM, Leleu X, Petillon MO, Karlin L, Doyen C, Demarquette H, Royer B, Macro M, Moreau P, Fostier K, Marie-Lorraine C, Zarnitsky C, Perrot A, Herbaux C, Poulain S, Manier S, Beauvais D, Walker BA, Wardell CP, Vincent L, Frenzel L, Caillon H, Susanna S, Dejoie T, Avet-Loiseau H, Mohty M, Facon T, IFM2014–04 investigators (2019) Daratumumab and dexamethasone is safe and effective for triple refractory myeloma patients: final results of the IFM 2014–04 (Etoile du Nord) trial. Br J Haematol 187:319–327

    CAS  Article  Google Scholar 

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Affiliations

  1. Multiple Myeloma GIMEMA Lazio Group, Via Casilina 5, 00182, Rome, Italy

    Federico Vozella, A. Siniscalchi, M. Rizzo, T. Za, G. Antolino, U. Coppetelli, A. Piciocchi, A. Andriani, O. Annibali, L. De Rosa, G. Cimino, G. La Verde, V. De Stefano, M. Cantonetti, T. Caravita di Toritto & M. T. Petrucci

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  1. Federico Vozella
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  2. A. Siniscalchi
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  3. M. Rizzo
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  4. T. Za
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  5. G. Antolino
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  6. U. Coppetelli
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  7. A. Piciocchi
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  8. A. Andriani
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  9. O. Annibali
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  10. L. De Rosa
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  11. G. Cimino
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  12. G. La Verde
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  13. V. De Stefano
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  14. M. Cantonetti
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Correspondence to Federico Vozella.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

  • F. Vozella has received grants/speaker honorarium from Amgen, Celgene, Takeda;

  • Siniscalchi declares that she has no conflict of interest;

  • M. Rizzo declares that she has no conflict of interest;

  • T. Za declares that he has no conflict of interest;

  • G. Antolino has received grants/speaker honorarium from Amgen, BMS, Celgene, Janssen-Cilag, Takeda;

  • U. Coppetelli declares that he has no conflict of interest;

  • Piciocchi declares that he has no conflict of interest;

  • Andriani has received grants/speaker honorarium from Abbvie, Celgene, Janssen-Cilag, Takeda;

  • O. Annibali has received grants/speaker honorarium from Amgen, Celgene, Janssen-Cilag, Roche, Takeda;

  • L. De Rosa has received grants/speaker honorarium from Amgen, Celgene, Janssen-Cilag, Roche, Takeda;

  • G. Cimino declares that he has no conflict of interest;

  • G. La Verde has received grants/speaker honorarium from Amgen, BMS, Celgene, Janssen-Cilag, Takeda;

  • V. De Stefano has received grants/speaker honorarium from AIFA, Alexion, Amgen, Bayer, Catholic University School of Medicine, Celgene, Janssen-Cilag, Novartis, Takeda;

  • M. Cantonetti has received grants/speaker honorarium from Gilead, Incyte, Janssen-Cilag, Kyowa Kirin, Mundipharma, Roche, Sandoz, Takeda, Vifor;

  • T. Caravita di Toritto has received grants/speaker honorarium from Amgen, Celgene, Janssen-Cilag, Takeda;

  • M.T. Petrucci has received grants/speaker honorarium from Amgen, Celgene, Janssen-Cilag, Takeda.

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Vozella, F., Siniscalchi, A., Rizzo, M. et al. Daratumumab in multiple myeloma: experience of the multiple myeloma GIMEMA Lazio group. Ann Hematol 100, 1059–1063 (2021). https://doi.org/10.1007/s00277-020-04374-y

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  • DOI: https://doi.org/10.1007/s00277-020-04374-y

Keywords

  • Multiple myeloma
  • Relapsed and refractory
  • Daratumumab
  • Immunotherapy