Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma
Open accessAbstract
BACKGROUND: The standard treatment for patients with multiple myeloma who are not candidates for high-dose therapy is melphalan and prednisone. This phase 3 study compared the use of melphalan and prednisone with or without bortezomib in previously untreated patients with multiple myeloma who were ineligible for high-dose therapy. METHODS: We randomly assigned 682 patients to receive nine 6-week cycles of melphalan (at a dose of 9 mg per square meter of body-surface area) and prednisone (at a dose of 60 mg per square meter) on days 1 to 4, either alone or with bortezomib (at a dose of 1.3 mg per square meter) on days 1, 4, 8, 11, 22, 25, 29, and 32 during cycles 1 to 4 and on days 1, 8, 22, and 29 during cycles 5 to 9. The primary end point was the time to disease progression. RESULTS: The time to progression among patients receiving bortezomib plus melphalan-prednisone (bortezomib group) was 24.0 months, as compared with 16.6 months among those receiving melphalan-prednisone alone (control group) (hazard ratio for the bortezomib group, 0.48; P<0.001). The proportions of patients with a partial response or better were 71% in the bortezomib group and 35% in the control group; complete-response rates were 30% and 4%, respectively (P<0.001). The median duration of the response was 19.9 months in the bortezomib group and 13.1 months in the control group. The hazard ratio for overall survival was 0.61 for the bortezomib group (P=0.008). Adverse events were consistent with established profiles of toxic events associated with bortezomib and melphalan-prednisone. Grade 3 events occurred in a higher proportion of patients in the bortezomib group than in the control group (53% vs. 44%, P=0.02), but there were no significant differences in grade 4 events (28% and 27%, respectively) or treatment-related deaths (1% and 2%). CONCLUSIONS: Bortezomib plus melphalan-prednisone was superior to melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy. (ClinicalTrials.gov number, NCT00111319.)
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
There is weak data suggesting that use of a proteasome inhibitor may abrogate the prognostic impact of at least some high-risk genetic markers.
“Albeit weak, there is data suggesting that use of a proteasome inhibitor may abrogate the prognostic impact of at least some of these high-risk genetic markers [32].”
From Epidemiology, Staging, and Management of Multiple Myeloma (2021) · cites this paper as [32]
Cited by
Sorted by citations
Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma
Attal, M., Lauwers-Cances, V., Hulin, C., Leleu, X., Caillot, D., Escoffre, M., Arnulf, B., Macro, M., Belhadj, K., Garderet, L., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611750 · Cited by 1,257 · see citing works
Self-citationInflammation and cancer: advances and new agents
Crusz, S. M., & Balkwill, F. R. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.105 · Cited by 1,184 · see citing works
Rajkumar, S. V., Harousseau, J.-L., Durie, B., Anderson, K. C., Dimopoulos, M., Kyle, R., Blade, J., Richardson, P., Orlowski, R., Siegel, D., et al. (2011) · Blood · doi:10.1182/blood-2010-10-299487 · Cited by 1,036 · see citing works
Self-citationProteasome inhibitors in cancer therapy
Manasanch, E. E., & Orlowski, R. Z. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.206 · Cited by 1,024 · see citing works
Rajkumar, S. V., Jacobus, S., Callander, N. S., Fonseca, R., Vesole, D. H., Williams, M. E., Abonour, R., Siegel, D. S., Katz, M., & Greipp, P. R. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70284-0 · Cited by 933 · see citing works
Durie, B. G. M., Hoering, A., Abidi, M. H., Rajkumar, S. V., Epstein, J., Kahanic, S. P., Thakuri, M., Reu, F., Reynolds, C. M., Sexton, R., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(16)31594-x · Cited by 908 · see citing works
Environment-mediated drug resistance: A major contributor to minimal residual disease
Meads, M. B., Gatenby, R. A., & Dalton, W. S. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2714 · Cited by 892 · see citing works
Richardson, P. G., Weller, E., Lonial, S., Jakubowiak, A. J., Jagannath, S., Raje, N. S., Avigan, D. E., Xie, W., Ghobrial, I. M., Schlossman, R. L., et al. (2010) · Blood · doi:10.1182/blood-2010-02-268862 · Cited by 861 · see citing works
Self-citationSonneveld, P., Schmidt-Wolf, I. G. H., van der Holt, B., el Jarari, L., Bertsch, U., Salwender, H., Zweegman, S., Vellenga, E., Broyl, A., Blau, I. W., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.39.6820 · Cited by 824 · see citing works
Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma
Benboubker, L., Dimopoulos, M. A., Dispenzieri, A., Catalano, J., Belch, A. R., Cavo, M., Pinto, A., Weisel, K., Ludwig, H., Bahlis, N., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1402551 · Cited by 793 · see citing works
Self-citationAutologous Transplantation and Maintenance Therapy in Multiple Myeloma
Palumbo, A., Cavallo, F., Gay, F., Di Raimondo, F., Ben Yehuda, D., Petrucci, M. T., Pezzatti, S., Caravita, T., Cerrato, C., Ribakovsky, E., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1402888 · Cited by 778 · see citing works
Self-citationKumar, S. K., Mikhael, J. R., Buadi, F. K., Dingli, D., Dispenzieri, A., Fonseca, R., Gertz, M. A., Greipp, P. R., Hayman, S. R., Kyle, R. A., et al. (2009) · Mayo Clinic Proceedings · doi:10.4065/mcp.2009.0603 · Cited by 628 · see citing works
Mateos, M.-V., Oriol, A., Martínez-López, J., Gutiérrez, N., Teruel, A.-I., de Paz, R., García-Laraña, J., Bengoechea, E., Martín, A., Mediavilla, J. D., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70187-x · Cited by 458 · see citing works
Self-citationPalumbo, A., Bringhen, S., Rossi, D., Cavalli, M., Larocca, A., Ria, R., Offidani, M., Patriarca, F., Nozzoli, C., Guglielmelli, T., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2010.29.8216 · Cited by 423 · see citing works
Self-citationMonoclonal antibodies targeting <scp>CD</scp>38 in hematological malignancies and beyond
van de Donk, N. W. C. J., Janmaat, M. L., Mutis, T., Lammerts van Bueren, J. J., Ahmadi, T., Sasser, A. K., Lokhorst, H. M., & Parren, P. W. H. I. (2016) · Immunological Reviews · doi:10.1111/imr.12389 · Cited by 353 · see citing works
Infections in Patients with Multiple Myeloma in the Era of High‐Dose Therapy and Novel Agents
Nucci, M., & Anaissie, E. (2009) · Clinical Infectious Diseases · doi:10.1086/605664 · Cited by 347 · see citing works
Zonder, J. A., Mohrbacher, A. F., Singhal, S., van Rhee, F., Bensinger, W. I., Ding, H., Fry, J., Afar, D. E. H., & Singhal, A. K. (2012) · Blood · doi:10.1182/blood-2011-06-360552 · Cited by 342 · see citing works
Epidemiology, Staging, and Management of Multiple Myeloma
Padala, S. A., Barsouk, A., Barsouk, A., Rawla, P., Vakiti, A., Kolhe, R., Kota, V., & Ajebo, G. H. (2021) · Medical Sciences · doi:10.3390/medsci9010003 · Cited by 332 · see citing works
“Albeit weak, there is data suggesting that use of a proteasome inhibitor may abrogate the prognostic impact of at least some of these high-risk genetic markers [32].”
BackgroundManagement of relapsed multiple myeloma: Recommendations of the International Myeloma Working Group
Laubach, J., Garderet, L., Mahindra, A., Gahrton, G., Caers, J., Sezer, O., Voorhees, P., Leleu, X., Johnsen, H. E., Streetly, M., et al. (2016) · Leukemia · doi:10.1038/leu.2015.356 · Cited by 258 · see citing works
Self-citationThe NEDD8 Conjugation Pathway and Its Relevance in Cancer Biology and Therapy
Soucy, T. A., Dick, L. R., Smith, P. G., Milhollen, M. A., & Brownell, J. E. (2010) · Genes & Cancer · doi:10.1177/1947601910382898 · Cited by 225 · see citing works
Goldschmidt, H., Lokhorst, H. M., Mai, E. K., van der Holt, B., Blau, I. W., Zweegman, S., Weisel, K. C., Vellenga, E., Pfreundschuh, M., Kersten, M. J., et al. (2018) · Leukemia · doi:10.1038/leu.2017.211 · Cited by 200 · see citing works
Rosiñol, L., Beksac, M., Zamagni, E., Van de Donk, N. W. C. J., Anderson, K. C., Badros, A., Caers, J., Cavo, M., Dimopoulos, M., Dispenzieri, A., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17338 · Cited by 179 · see citing works
Self-citationRichardson, P. G., Weller, E., Jagannath, S., Avigan, D. E., Alsina, M., Schlossman, R. L., Mazumder, A., Munshi, N. C., Ghobrial, I. M., Doss, D., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.22.2679 · Cited by 162 · see citing works
Self-citationAssociation of response endpoints with survival outcomes in multiple myeloma
Lonial, S., & Anderson, K. C. (2014) · Leukemia · doi:10.1038/leu.2013.220 · Cited by 162 · see citing works
Self-citationMultiple myeloma: 2011 update on diagnosis, risk-stratification, and management
Rajkumar, S. V. (2011) · American Journal of Hematology · doi:10.1002/ajh.21913 · Cited by 152 · see citing works
Palumbo, A., Gay, F., Cavallo, F., Di Raimondo, F., Larocca, A., Hardan, I., Nagler, A., Petrucci, M. T., Hajek, R., Pezzatti, S., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.60.2466 · Cited by 150 · see citing works
Self-citationPillarisetti, K., Powers, G., Luistro, L., Babich, A., Baldwin, E., Li, Y., Zhang, X., Mendonça, M., Majewski, N., Nanjunda, R., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020002393 · Cited by 144 · see citing works
How I treat multiple myeloma in younger patients
Stewart, A. K., Richardson, P. G., & San-Miguel, J. F. (2009) · Blood · doi:10.1182/blood-2009-07-204651 · Cited by 133 · see citing works
Self-citationArnulf, B., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., van de Velde, H., Feng, H., Cakana, A., Deraedt, W., & Moreau, P. (2012) · Haematologica · doi:10.3324/haematol.2012.067793 · Cited by 127 · see citing works
Self-citationAscorbic acid inhibits antitumor activity of bortezomib in vivo
Perrone, G., Hideshima, T., Ikeda, H., Okawa, Y., Calabrese, E., Gorgun, G., Santo, L., Cirstea, D., Raje, N., Chauhan, D., et al. (2009) · Leukemia · doi:10.1038/leu.2009.83 · Cited by 109 · see citing works
Self-citationHerpes Zoster: Diagnostic, Therapeutic, and Preventive Approaches
Bader, M. S. (2013) · Postgraduate Medicine · doi:10.3810/pgm.2013.09.2703 · Cited by 90 · see citing works
Clinical use of proteasome inhibitors in the treatment of multiple myeloma
Merin, N., & Kelly, K. (2014) · Pharmaceuticals · doi:10.3390/ph8010001 · Cited by 90 · see citing works
The application and biology of immunomodulatory drugs (IMiDs) in cancer
Pan, B., & Lentzsch, S. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.004 · Cited by 76 · see citing works
Safety of proteasome inhibitors for treatment of multiple myeloma
Schlafer, D., Shah, K. S., Panjic, E. H., & Lonial, S. (2016) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2017.1259310 · Cited by 71 · see citing works
Huang, S.-Y., Lin, C.-W., Lin, H.-H., Yao, M., Tang, J.-L., Wu, S.-J., Chen, Y.-C., Lu, H.-Y., Hou, H.-A., Chen, C.-Y., et al. (2014) · Annals of Hematology · doi:10.1007/s00277-014-2063-7 · Cited by 62 · see citing works
Multiple Myeloma: From Front-Line to Relapsed Therapies
Moreau, P., & Touzeau, C. (2015) · American Society of Clinical Oncology Educational Book · doi:10.14694/edbook_am.2015.35.e504 · Cited by 48 · see citing works
Costa, B. A., Mouhieddine, T. H., Ortiz, R. J., & Richter, J. (2023) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2023.104040 · Cited by 18 · see citing works
- Authors
- San Miguel, J. F., Schlag, R., Khuageva, N. K., Dimopoulos, M. A., Shpilberg, O., Kropff, M., Spicka, I., Petrucci, M. T., Palumbo, A., Samoilova, O. S., Dmoszynska, A., Abdulkadyrov, K. M., Schots, R., Jiang, B., Mateos, M.-V., Anderson, K. C., Esseltine, D. L., Liu, K., Cakana, A., van de Velde, H., & Richardson, P. G.
- Affiliations
- Belgian Hematological Society (BE)
- Botkin Hospital (RU)
- National and Kapodistrian University of Athens (GR)
- Rabin Medical Center (IL)
- University of Münster (DE)
- Sapienza University of Rome (IT)
- University of Turin (IT)
- Nizhny Novgorod Regional Clinical Hospital named after Semashko (RU)
- Russian Research Institute of Hematology and Transfusiology (RU)
- Peking University (CN)
- Dana-Farber Cancer Institute (US)
- Takeda Oncology (United States) (US)
- Johnson & Johnson (United States) (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2008-08-28
- Volume
- 359
- Issue
- 9
- Pages
- 906-917
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2096207943
- Cited by
- 1,899
- References
- 0
- Citations by year
- 2026: 19 · 2025: 30 · 2024: 26 · 2023: 63 · 2022: 56 · 2021: 83 · 2020: 90 · 2019: 91 · 2018: 94 · 2017: 118 · 2016: 115 · 2015: 132 · 2014: 144 · 2013: 164 · 2012: 172
- FWCI
- 108.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- Gredos (University of Salamanca) (submittedVersion, cc-by-nc-nd)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- American Society of Hematology
- Celgene
- Takeda Oncology
- Cilag
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- multiple myeloma, bortezomib, melphalan, prednisone, combination chemotherapy, treatment-naive patients, time to progression, overall survival, complete response, adverse events, proteasome inhibitors, treatment response duration, non-relapse mortality, neuropathy, neutropenia, thrombocytopenia
- MeSH terms
- Bortezomib, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Boronic Acids, Female, Follow-Up Studies, Humans, Male, Melphalan, Middle Aged, Multiple Myeloma, Prednisone, Pyrazines, Time Factors, Survival Analysis, Treatment Outcome, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
