Overall Survival With Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial
Open accessAbstract
PURPOSE: With the initial analysis of POLLUX at a median follow-up of 13.5 months, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the time of final analysis for overall survival (OS). METHODS: POLLUX was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned 1:1 to D-Rd or Rd until disease progression or unacceptable toxicity. After positive primary analysis and protocol amendment, patients receiving Rd were offered daratumumab monotherapy after disease progression. RESULTS: Significant OS benefit was observed with D-Rd (hazard ratio, 0.73; 95% CI, 0.58 to 0.91; P = .0044) at a median (range) follow-up of 79.7 months (0.0-86.5). The median OS was 67.6 months for D-Rd compared with 51.8 months for Rd. Prespecified analyses demonstrated an improved OS with D-Rd versus Rd in most subgroups, including patients age ≥ 65 years and patients with one, two, or three prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and refractoriness to their last prior line of therapy or a proteasome inhibitor. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Rd versus Rd were neutropenia (57.6% v 41.6%), anemia (19.8% v 22.4%), pneumonia (17.3% v 11.0%), thrombocytopenia (15.5% v 15.7%), and diarrhea (10.2% v 3.9%). CONCLUSION: D-Rd significantly extended OS versus Rd alone in patients with RRMM. To our knowledge, for the first time, our findings, together with the OS benefit observed with daratumumab plus bortezomib and dexamethasone in the phase III CASTOR trial, demonstrate OS improvement with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02076009 [POLLUX]).
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In the POLLUX trial, daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly extended overall survival compared to Rd in relapsed/refractory multiple myeloma patients (67.6 vs 51.8 months).
“In the POLLUX phase 3 trial, the median OS was 67.6 months for D-Rd compared with 51.8 months for Rd, D-Rd significantly extended OS compared to Rd alone in patients with RRMM [162].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [162]
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Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.
Dimopoulos, M. A., Oriol, A., Nahi, H., San-Miguel, J., Bahlis, N. J., Usmani, S. Z., Rabin, N., Orlowski, R. Z., Komarnicki, M., Suzuki, K., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607751 · Cited by 1,445 · cited 1× · see citing works
“0 (1-63) cycles; the median (range) duration of daratumumab monotherapy was 5.”
BackgroundSelf-citationDaratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma
Facon, T., Kumar, S., Plesner, T., Orlowski, R. Z., Moreau, P., Bahlis, N., Basu, S., Nahi, H., Hulin, C., Quach, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1817249 · Cited by 1,027 · cited 2× · see citing works
“0 (1-63) cycles; the median (range) duration of daratumumab monotherapy was 5.”
BackgroundSelf-citationLammerts van Bueren, J., Jakobs, D., Kaldenhoven, N., Roza, M., Hiddingh, S., Meesters, J., Voorhorst, M., Gresnigt, E., Wiegman, L., Ortiz Buijsse, A., et al. (2014) · Blood · doi:10.1182/blood.v124.21.3474.3474 · Cited by 222 · see citing works
Fonseca, R., Usmani, S. Z., Mehra, M., Slavcev, M., He, J., Cote, S., Lam, A., Ukropec, J., Maiese, E. M., Nair, S., et al. (2020) · BMC Cancer · doi:10.1186/s12885-020-07503-y · Cited by 127 · see citing works
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Research works printed but not linked: 21
- [1]de Weers M Tai YT van der Veer MS: Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 186: 1840- 1848, 2011 21187443
- [3]Overdijk MB Verploegen S Bogels M: Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs 7: 311- 321, 2015 25760767 PMC4622648
- [4]Overdijk MB Jansen JH Nederend M: The therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via Fcgamma receptor-mediated cross-linking. J Immunol 197: 807- 813, 2016 27316683
- [5]Krejcik J Casneuf T Nijhof IS: Daratumumab depletes CD38+ immune-regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood 128: 384- 394, 2016 27222480 PMC4957162
- [6]Adams HC III Stevenaert F Krejcik J: High-parameter mass cytometry evaluation of relapsed/refractory multiple myeloma patients treated with daratumumab demonstrates immune modulation as a novel mechanism of action. Cytometry A 95: 279- 289, 2019 30536810 PMC6590645
- [7]Casneuf T Adams HC III van de Donk NWCJ: Deep immune profiling of patients treated with lenalidomide and dexamethasone with or without daratumumab. Leukemia 35: 573- 584, 2021 32457357 PMC7862054
- [8]Kinder M Bahlis NJ Malavasi F: Comparison of CD38 antibodies in vitro and ex vivo mechanisms of action in multiple myeloma. Haematologica 106: 2004- 2008, 2021 33440920 PMC8252955
- [9]Moreau P Attal M Hulin C: 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 394: 29- 38, 2019 31171419
- [10]Mateos MV Cavo M Blade J: Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): A randomised, open-label, phase 3 trial. Lancet 395: 132- 141, 2020 31836199
- [12]Mateos MV Sonneveld P Hungria V: Daratumumab, bortezomib, and dexamethasone versus bortezomib and dexamethasone in patients with previously treated multiple myeloma: Three-year follow-up of CASTOR. Clin Lymphoma Myeloma Leuk 20: 509- 518, 2020 32482541
- [13]Bahlis NJ Dimopoulos MA White DJ: Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 34: 1875- 1884, 2020 32001798 PMC7326710
- [14]Dimopoulos MA Terpos E Boccadoro M: Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): An open-label, randomised, phase 3 trial. Lancet Oncol 22: 801- 812, 2021 34087126
- [18]Dimopoulos M San Miguel J Belch A: Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: Updated analysis of POLLUX. Haematologica 103: 2088- 2096, 2018 30237262 PMC6269302
- [20]Durie BGM Harousseau JL Miguel JS: International uniform response criteria for multiple myeloma. Leukemia 20: 1467- 1473, 2006 16855634
- [21]Rajkumar SV Harousseau JL Durie B: Consensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1. Blood 117: 4691- 4695, 2011 21292775 PMC3710442
- [22]Sonneveld P Chanan-Khan A Weisel K: Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): A randomized, open-label, phase III trial. J Clin Oncol 41: 1600- 1609, 2023 36413710 PMC10022857
- [23]Richardson PG Kumar SK Masszi T: Final overall survival analysis of the TOURMALINE-MM1 phase III trial of ixazomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol 39: 2430- 2442, 2021 34111952
- [24]Siegel DS Dimopoulos MA Ludwig H: Improvement in overall survival with carfilzomib, lenalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma. J Clin Oncol 36: 728- 734, 2018 29341834
- [25]Dimopoulos MA Lonial S White D: Elotuzumab, lenalidomide, and dexamethasone in RRMM: Final overall survival results from the phase 3 randomized ELOQUENT-2 study. Blood Cancer J 10: 91, 2020 32887873 PMC7474076
- [26]Facon T Kumar SK Plesner T: Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): Overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 22: 1582- 1596, 2021 34655533
- [27]Yong K Delforge M Driessen C: Multiple myeloma: Patient outcomes in real-world practice. Br J Haematol 175: 252- 264, 2016 27411022 PMC5096152
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Multiple myeloma: signaling pathways and targeted therapy
Lu, Q., Yang, D., Li, H., Niu, T., & Tong, A. (2024) · Molecular biomedicine · doi:10.1186/s43556-024-00188-w · Cited by 90 · see citing works
Hungria, V., Robak, P., Hus, M., Zherebtsova, V., Ward, C., Ho, P. J., Hájek, R., Kim, K., Grosicki, S., Sia, H., et al. (2025) · The Lancet Oncology · doi:10.1016/s1470-2045(25)00330-4 · Cited by 35 · see citing works
Self-citation
- Authors
- Dimopoulos, M. A., Oriol, A., Nahi, H., San-Miguel, J., Bahlis, N. J., Usmani, S. Z., Rabin, N., Orlowski, R. Z., Suzuki, K., Plesner, T., Yoon, S.-S., Ben Yehuda, D., Richardson, P. G., Goldschmidt, H., Reece, D., Ahmadi, T., Qin, X., Garvin Mayo, W., Gai, X., Carey, J., Carson, R., & Moreau, P.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Josep Carreras Leukaemia Research Institute (ES)
- Karolinska University Hospital (SE)
- Clínica Universidad de Navarra, CCUN, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), CIBER-ONC, Pamplona, Spain
- University of Calgary (CA)
- Memorial Sloan Kettering Cancer Center (US)
- University College Hospital (GB)
- The University of Texas MD Anderson Cancer Center (US)
- Japanese Red Cross Medical Center (JP)
- University of Southern Denmark (DK)
- Seoul National University (KR)
- Hematology Department, Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel
- Harvard University (US)
- University Hospital Heidelberg (DE)
- Princess Margaret Cancer Centre (CA)
- Genmab (United States) (US)
- Janssen Research & Development, LLC, Spring House, PA
- Janssen Research & Development, LLC, Raritan, NJ
- Janssen Research & Development, LLC, Beijing, China
- Nantes Université (FR)
- Corresponding author
- Dimopoulos, Meletios A.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2023-03-10
- Volume
- 41
- Issue
- 8
- Pages
- 1590-1599
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC10022849
- OpenAlex
- W4313544410
- Cited by
- 140
- References
- 4
- Citations by year
- 2026: 28 · 2025: 47 · 2024: 41 · 2023: 23 · 2022: 1
- FWCI
- 28.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion, cc-by-nc-nd)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, cc-by-nc-nd)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
- Digital Commons-TMC (Texas Medical Center) (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- relapsed multiple myeloma, daratumumab, lenalidomide, dexamethasone, relapsed/refractory multiple myeloma, overall survival, progression-free survival, treatment-emergent adverse events, neutropenia, chromosomal abnormalities
- MeSH terms
- Lenalidomide, Aged, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Dexamethasone, Humans, Multiple Myeloma, Disease Progression
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