Daratumumab, bortezomib, and dexamethasone for multiple myeloma

A. A. Palumbo, Asher A. Chanan-Khan, Katja Weisel, Ajay K. Nooka, T. Masszi, M. Beksac, Ivan Spicka, Vania Hungria, Markus Munder, Maria Victoria Mateos, Tomer M Mark, Ming Qi, Jordan Schecter, Himal Amin, Xiang Qin, William Deraedt, Tahamtan Ahmadi, Craig A. Spencer, P. Sonneveld, Nicola Cascavilla

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P
Original languageEnglish
Pages (from-to)754-766
Number of pages13
JournalNew England Journal of Medicine
Volume375
Issue number8
DOIs
Publication statusPublished - 2016

Fingerprint

Multiple Myeloma
Dexamethasone
Disease-Free Survival
Control Groups
Body Surface Area
Bortezomib
daratumumab
Immunoglobulin G
Monoclonal Antibodies
Body Weight
Confidence Intervals

Keywords

  • antineoplastic agent
  • bortezomib
  • CD38 antigen
  • daratumumab
  • dexamethasone
  • monoclonal antibody
  • adult
  • aged
  • antagonists and inhibitors
  • clinical trial
  • controlled study
  • disease free survival
  • drug resistance
  • female
  • human
  • intravenous drug administration
  • male
  • middle aged
  • multicenter study
  • multiple myeloma
  • phase 3 clinical trial
  • randomized controlled trial
  • recurrent disease
  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Antigens, CD38
  • Antineoplastic Combined Chemotherapy Protocols
  • Bortezomib
  • Dexamethasone
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Multiple Myeloma
  • Recurrence

Cite this

Palumbo, A. A., Chanan-Khan, A. A., Weisel, K., Nooka, A. K., Masszi, T., Beksac, M., ... Cascavilla, N. (2016). Daratumumab, bortezomib, and dexamethasone for multiple myeloma. New England Journal of Medicine, 375(8), 754-766. https://doi.org/10.1056/NEJMoa1606038

Daratumumab, bortezomib, and dexamethasone for multiple myeloma. / Palumbo, A. A.; Chanan-Khan, Asher A.; Weisel, Katja; Nooka, Ajay K.; Masszi, T.; Beksac, M.; Spicka, Ivan; Hungria, Vania; Munder, Markus; Mateos, Maria Victoria; Mark, Tomer M; Qi, Ming; Schecter, Jordan; Amin, Himal; Qin, Xiang; Deraedt, William; Ahmadi, Tahamtan; Spencer, Craig A.; Sonneveld, P.; Cascavilla, Nicola.

In: New England Journal of Medicine, Vol. 375, No. 8, 2016, p. 754-766.

Research output: Contribution to journalArticle

Palumbo, AA, Chanan-Khan, AA, 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, CA, Sonneveld, P & Cascavilla, N 2016, 'Daratumumab, bortezomib, and dexamethasone for multiple myeloma', New England Journal of Medicine, vol. 375, no. 8, pp. 754-766. https://doi.org/10.1056/NEJMoa1606038
Palumbo AA, Chanan-Khan AA, Weisel K, Nooka AK, Masszi T, Beksac M et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. New England Journal of Medicine. 2016;375(8):754-766. https://doi.org/10.1056/NEJMoa1606038
Palumbo, A. A. ; Chanan-Khan, Asher A. ; Weisel, Katja ; Nooka, Ajay K. ; Masszi, T. ; Beksac, M. ; Spicka, Ivan ; Hungria, Vania ; Munder, Markus ; Mateos, Maria Victoria ; Mark, Tomer M ; Qi, Ming ; Schecter, Jordan ; Amin, Himal ; Qin, Xiang ; Deraedt, William ; Ahmadi, Tahamtan ; Spencer, Craig A. ; Sonneveld, P. ; Cascavilla, Nicola. / Daratumumab, bortezomib, and dexamethasone for multiple myeloma. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 8. pp. 754-766.
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title = "Daratumumab, bortezomib, and dexamethasone for multiple myeloma",
abstract = "BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7{\%} in the daratumumab group versus 26.9{\%} in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95{\%} confidence interval, 0.28 to 0.53; P",
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author = "Palumbo, {A. A.} and Chanan-Khan, {Asher A.} and Katja Weisel and Nooka, {Ajay K.} and T. Masszi and M. Beksac and Ivan Spicka and Vania Hungria and Markus Munder and Mateos, {Maria Victoria} and Mark, {Tomer M} and Ming Qi and Jordan Schecter and Himal Amin and Xiang Qin and William Deraedt and Tahamtan Ahmadi and Spencer, {Craig A.} and P. Sonneveld and Nicola Cascavilla",
note = "Cited By :28 Export Date: 22 March 2017 CODEN: NEJMA Correspondence Address: Palumbo, A.; Department of Hematology, University of Turin, Via Genova 3, Italy; email: appalumbo@yahoo.com Chemicals/CAS: bortezomib, 179324-69-7, 197730-97-5; daratumumab, 945721-28-8; dexamethasone, 50-02-2; Antibodies, Monoclonal; Antigens, CD38; Bortezomib; daratumumab; Dexamethasone Funding details: Janssen Research and Development Funding text: (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT02136134.) Supported by Janssen Research and Development. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients who volunteered to participate in this trial and the staff members at the trial sites who cared for them; the members of the data and safety monitoring committee (Amrita Krishnan, M.D. [chair]; Helmut Ostermann, M.D.; and Yu Shyr, Ph.D. [statistician]); representatives of the sponsor who were involved in data collection and analyses (in particular, Brian Berkey, Chris Velas, Nele Boeykens, Dorien Druyts, and Ward Lemaire); and Jason Jung, Ph.D., and Christopher Jones, Ph.D., of MedErgy, for editorial assistance in the development of an earlier draft of the manuscript. References: R{\"o}llig, C., Knop, S., Bornh{\"a}user, M., Multiple myeloma (2015) Lancet, 385, pp. 2197-2208; Rajkumar, S.V., Kumar, S., Multiple myeloma: Diagnosis and treatment (2016) Mayo Clin Proc, 91, pp. 101-119; Anderson, K.C., Alsina, M., Atanackovic, D., NCCN guidelines insights: Multiple myeloma (2016) J Natl Compr Canc Netw, 14, pp. 389-400. , version 3.2016; Robinson, R., Kaura, S., Kiely, D., Hussein, M.A., Nersesyan, K., Durie, B.G., Impact of novel treatments on multiple myeloma survival (2014) Blood, 124, p. 5676; Santonocito, A.M., Consoli, U., Bagnato, S., Flow cytometric detection of aneuploid CD38(++) plasmacells and CD19(+) B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients (2004) Leuk Res, 28, pp. 469-477; 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, pp. 482-488; Lammerts Van Bueren, J.J., Jakobs, D., Kaldenhoven, N., Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79 (2014) American Society of Hematology 56th Annual Meeting and Exposition, , San Francisco, December 6-9, abstract; Jansen, J.H.M., Boross, P., Overdijk, M.B., Lammerts Van Bueren, J.J., Parren, P.W.H.I., Leusen, H.H.W., Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking (2012) American Society of Hematology 54th Annual Meeting and Exposition, , Atlanta, December 8-11, abstract; De Weers, M., Tai, Y.T., Van Der Veer, M.S., Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors (2011) J Immunol, 186, pp. 1840-1848; Overdijk, M.B., Verploegen, S., B{\"o}gels, M., Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma (2015) MAbs, 7, pp. 311-321; Krejcik, J., Casneuf, T., Nijhof, I.S., Daratumumab depletes CD38+ immuneregulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma (2016) Blood, 128, pp. 384-394; Usmani, S.Z., Weiss, B.M., Plesner, T., Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma (2016) Blood, 128, pp. 37-44; McKeage, K., Daratumumab: First global approval (2016) Drugs, 76, pp. 275-281; Mateos, M.V., Moreau, P., Comenzo, R., An open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide-dexamethasone and with backbone regimens in patients with multiple myeloma (2015) 20th Congress of the European Hematology Association, , Vienna, June 11-14; Chari, A., Lonial, S., Suvannasankha, A., 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 (MM) (2015) American Society of Hematology 56th Annual Meeting and Exposition, , San Francisco, December 6-9; Durie, B.G., Harousseau, J.L., Miguel, J.S., International uniform response criteria for multiple myeloma (2006) Leukemia, 20, pp. 1467-1473; Rajkumar, S.V., Harousseau, J.L., Durie, B., Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1 (2011) Blood, 117, pp. 4691-4695; Richardson, P.G., Barlogie, B., Berenson, J., A phase 2 study of bortezomib in relapsed, refractory myeloma (2003) N Engl J Med, 348, pp. 2609-2617; Lonial, S., Weiss, B.M., Usmani, S.Z., Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial (2016) Lancet, 387, pp. 1551-1560; Durie, B.G., Miguel, J.F., Blade, J., Rajkumar, S.V., Clarification of the definition of complete response in multiple myeloma (2015) Leukemia, 29, pp. 2416-2417; McCudden, C., Axel, A.E., Slaets, D., Monitoring multiple myeloma patients treated with daratumumab: Teasing out monoclonal antibody interference (2016) Clin Chem Lab Med, 54, pp. 1095-1104; DeMets, D.L., Lan, G., The alpha spending function approach to interim data analyses (1995) Cancer Treat Res, 75, pp. 1-27; Lan, K.K.G., DeMets, D.L., Discrete sequential boundaries for clinical trials (1983) Biometrika, 70, pp. 659-663; Plesner, T., Arkenau, H.T., Lokhorst, H.M., Daratumumab 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) (2015) American Society of Hematology 57th Annual Meeting and Exposition, , Orlando, FL, December 5-8, abstract; Lonial, S., Mitsiades, C.S., Richardson, P.G., Treatment options for relapsed and refractory multiple myeloma (2011) Clin Cancer Res, 17, pp. 1264-1277; Endell, J., Samuelsson, C., Boxhammer, R., Strauss, S., Steidl, S., Effect of MOR202, a human CD38 antibody, in combination with lenalidomide and bortezomib, on bone lysis and tumor load in a physiologic model of myeloma (2011) 2011 American Society of Clinical Oncology Annual Meeting, , Chicago, June 3-7, abstract; Van Der Veer, M.S., De Weers, M., Van Kessel, B., The therapeutic human CD38 antibody daratumumab improves the antimyeloma effect of newly emerging multidrug therapies (2011) Blood Cancer J, 1 (10), p. e41; Dimopoulos, M.A., Richardson, P.G., Moreau, P., Anderson, K.C., Current treatment landscape for relapsed and/or refractory multiple myeloma (2015) Nat Rev Clin Oncol, 12, pp. 42-54; Dimopoulos, M.A., Moreau, P., Palumbo, A., Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study (2016) Lancet Oncol, 17, pp. 27-38; San-Miguel, J.F., Hungria, V.T., Yoon, S.S., Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial (2014) Lancet Oncol, 15, pp. 1195-1206; Jakubowiak, A., Offidani, M., P{\'e}gourie, B., Randomized phase 2 study: Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM (2016) Blood, 127, pp. 2833-2840; Lokhorst, H.M., Plesner, T., Laubach, J.P., Targeting CD38 with daratumumab monotherapy in multiple myeloma (2015) N Engl J Med, 373, pp. 1207-1219",
year = "2016",
doi = "10.1056/NEJMoa1606038",
language = "English",
volume = "375",
pages = "754--766",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "8",

}

TY - JOUR

T1 - Daratumumab, bortezomib, and dexamethasone for multiple myeloma

AU - Palumbo, A. A.

AU - Chanan-Khan, Asher A.

AU - Weisel, Katja

AU - Nooka, Ajay K.

AU - Masszi, T.

AU - Beksac, M.

AU - Spicka, Ivan

AU - Hungria, Vania

AU - Munder, Markus

AU - Mateos, Maria Victoria

AU - Mark, Tomer M

AU - Qi, Ming

AU - Schecter, Jordan

AU - Amin, Himal

AU - Qin, Xiang

AU - Deraedt, William

AU - Ahmadi, Tahamtan

AU - Spencer, Craig A.

AU - Sonneveld, P.

AU - Cascavilla, Nicola

N1 - Cited By :28 Export Date: 22 March 2017 CODEN: NEJMA Correspondence Address: Palumbo, A.; Department of Hematology, University of Turin, Via Genova 3, Italy; email: appalumbo@yahoo.com Chemicals/CAS: bortezomib, 179324-69-7, 197730-97-5; daratumumab, 945721-28-8; dexamethasone, 50-02-2; Antibodies, Monoclonal; Antigens, CD38; Bortezomib; daratumumab; Dexamethasone Funding details: Janssen Research and Development Funding text: (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT02136134.) Supported by Janssen Research and Development. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients who volunteered to participate in this trial and the staff members at the trial sites who cared for them; the members of the data and safety monitoring committee (Amrita Krishnan, M.D. [chair]; Helmut Ostermann, M.D.; and Yu Shyr, Ph.D. [statistician]); representatives of the sponsor who were involved in data collection and analyses (in particular, Brian Berkey, Chris Velas, Nele Boeykens, Dorien Druyts, and Ward Lemaire); and Jason Jung, Ph.D., and Christopher Jones, Ph.D., of MedErgy, for editorial assistance in the development of an earlier draft of the manuscript. References: Röllig, C., Knop, S., Bornhäuser, M., Multiple myeloma (2015) Lancet, 385, pp. 2197-2208; Rajkumar, S.V., Kumar, S., Multiple myeloma: Diagnosis and treatment (2016) Mayo Clin Proc, 91, pp. 101-119; Anderson, K.C., Alsina, M., Atanackovic, D., NCCN guidelines insights: Multiple myeloma (2016) J Natl Compr Canc Netw, 14, pp. 389-400. , version 3.2016; Robinson, R., Kaura, S., Kiely, D., Hussein, M.A., Nersesyan, K., Durie, B.G., Impact of novel treatments on multiple myeloma survival (2014) Blood, 124, p. 5676; Santonocito, A.M., Consoli, U., Bagnato, S., Flow cytometric detection of aneuploid CD38(++) plasmacells and CD19(+) B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients (2004) Leuk Res, 28, pp. 469-477; 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, pp. 482-488; Lammerts Van Bueren, J.J., Jakobs, D., Kaldenhoven, N., Direct in vitro comparison of daratumumab with surrogate analogs of CD38 antibodies MOR03087, SAR650984 and Ab79 (2014) American Society of Hematology 56th Annual Meeting and Exposition, , San Francisco, December 6-9, abstract; Jansen, J.H.M., Boross, P., Overdijk, M.B., Lammerts Van Bueren, J.J., Parren, P.W.H.I., Leusen, H.H.W., Daratumumab, a human CD38 antibody induces apoptosis of myeloma tumor cells via Fc receptor-mediated crosslinking (2012) American Society of Hematology 54th Annual Meeting and Exposition, , Atlanta, December 8-11, abstract; De Weers, M., Tai, Y.T., Van Der Veer, M.S., Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors (2011) J Immunol, 186, pp. 1840-1848; Overdijk, M.B., Verploegen, S., Bögels, M., Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma (2015) MAbs, 7, pp. 311-321; Krejcik, J., Casneuf, T., Nijhof, I.S., Daratumumab depletes CD38+ immuneregulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma (2016) Blood, 128, pp. 384-394; Usmani, S.Z., Weiss, B.M., Plesner, T., Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma (2016) Blood, 128, pp. 37-44; McKeage, K., Daratumumab: First global approval (2016) Drugs, 76, pp. 275-281; Mateos, M.V., Moreau, P., Comenzo, R., An open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide-dexamethasone and with backbone regimens in patients with multiple myeloma (2015) 20th Congress of the European Hematology Association, , Vienna, June 11-14; Chari, A., Lonial, S., Suvannasankha, A., 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 (MM) (2015) American Society of Hematology 56th Annual Meeting and Exposition, , San Francisco, December 6-9; Durie, B.G., Harousseau, J.L., Miguel, J.S., International uniform response criteria for multiple myeloma (2006) Leukemia, 20, pp. 1467-1473; Rajkumar, S.V., Harousseau, J.L., Durie, B., Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1 (2011) Blood, 117, pp. 4691-4695; Richardson, P.G., Barlogie, B., Berenson, J., A phase 2 study of bortezomib in relapsed, refractory myeloma (2003) N Engl J Med, 348, pp. 2609-2617; Lonial, S., Weiss, B.M., Usmani, S.Z., Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): An open-label, randomised, phase 2 trial (2016) Lancet, 387, pp. 1551-1560; Durie, B.G., Miguel, J.F., Blade, J., Rajkumar, S.V., Clarification of the definition of complete response in multiple myeloma (2015) Leukemia, 29, pp. 2416-2417; McCudden, C., Axel, A.E., Slaets, D., Monitoring multiple myeloma patients treated with daratumumab: Teasing out monoclonal antibody interference (2016) Clin Chem Lab Med, 54, pp. 1095-1104; DeMets, D.L., Lan, G., The alpha spending function approach to interim data analyses (1995) Cancer Treat Res, 75, pp. 1-27; Lan, K.K.G., DeMets, D.L., Discrete sequential boundaries for clinical trials (1983) Biometrika, 70, pp. 659-663; Plesner, T., Arkenau, H.T., Lokhorst, H.M., Daratumumab 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) (2015) American Society of Hematology 57th Annual Meeting and Exposition, , Orlando, FL, December 5-8, abstract; Lonial, S., Mitsiades, C.S., Richardson, P.G., Treatment options for relapsed and refractory multiple myeloma (2011) Clin Cancer Res, 17, pp. 1264-1277; Endell, J., Samuelsson, C., Boxhammer, R., Strauss, S., Steidl, S., Effect of MOR202, a human CD38 antibody, in combination with lenalidomide and bortezomib, on bone lysis and tumor load in a physiologic model of myeloma (2011) 2011 American Society of Clinical Oncology Annual Meeting, , Chicago, June 3-7, abstract; Van Der Veer, M.S., De Weers, M., Van Kessel, B., The therapeutic human CD38 antibody daratumumab improves the antimyeloma effect of newly emerging multidrug therapies (2011) Blood Cancer J, 1 (10), p. e41; Dimopoulos, M.A., Richardson, P.G., Moreau, P., Anderson, K.C., Current treatment landscape for relapsed and/or refractory multiple myeloma (2015) Nat Rev Clin Oncol, 12, pp. 42-54; Dimopoulos, M.A., Moreau, P., Palumbo, A., Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre study (2016) Lancet Oncol, 17, pp. 27-38; San-Miguel, J.F., Hungria, V.T., Yoon, S.S., Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: A multicentre, randomised, double-blind phase 3 trial (2014) Lancet Oncol, 15, pp. 1195-1206; Jakubowiak, A., Offidani, M., Pégourie, B., Randomized phase 2 study: Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM (2016) Blood, 127, pp. 2833-2840; Lokhorst, H.M., Plesner, T., Laubach, J.P., Targeting CD38 with daratumumab monotherapy in multiple myeloma (2015) N Engl J Med, 373, pp. 1207-1219

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P

AB - BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival. RESULTS: A prespecified interim analysis showed that the rate of progression-free survival was significantly higher in the daratumumab group than in the control group; the 12-month rate of progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group. After a median follow-up period of 7.4 months, the median progression-free survival was not reached in the daratumumab group and was 7.2 months in the control group (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval, 0.28 to 0.53; P

KW - antineoplastic agent

KW - bortezomib

KW - CD38 antigen

KW - daratumumab

KW - dexamethasone

KW - monoclonal antibody

KW - adult

KW - aged

KW - antagonists and inhibitors

KW - clinical trial

KW - controlled study

KW - disease free survival

KW - drug resistance

KW - female

KW - human

KW - intravenous drug administration

KW - male

KW - middle aged

KW - multicenter study

KW - multiple myeloma

KW - phase 3 clinical trial

KW - randomized controlled trial

KW - recurrent disease

KW - Adult

KW - Aged

KW - Antibodies, Monoclonal

KW - Antigens, CD38

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Bortezomib

KW - Dexamethasone

KW - Disease-Free Survival

KW - Drug Resistance, Neoplasm

KW - Female

KW - Humans

KW - Infusions, Intravenous

KW - Male

KW - Middle Aged

KW - Multiple Myeloma

KW - Recurrence

U2 - 10.1056/NEJMoa1606038

DO - 10.1056/NEJMoa1606038

M3 - Article

VL - 375

SP - 754

EP - 766

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 8

ER -