Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma

Blood

Volumn 123, Issue 26, 2014, Pages 4136-4142

  San Miguel, Jesús ^a   Bladé, Joan ^b   Shpilberg, Ofer ^c   Grosicki, Sebastian ^d   Maloisel, Frédéric ^e   Min, Chang Ki ^f   Zarzuela, Marta Polo ^g   Robak, Tadeusz ^h   Prasad, Sripada V S S ⁱ   Goh, Yeow Tee ^j   Laubach, Jacob ^k   Spencer, Andrew ^l   Mateos, María Victoria ^m   Palumbo, Antonio ⁿ   Puchalski, Tom ^o   Reddy, Manjula ^o   Uhlar, Clarissa ^o   Qin, Xiang ^o   Van De Velde, Helgi ^o   Xie, Hong ^o   Orlowski, Robert Z ^p   more..

^a UNIVERSITY OF NAVARRA   (Spain)

^b HOSPITAL CLÍNIC   (Spain)

^c TEL AVIV UNIVERSITY   (Israel)

^d Oddzial Hematologiczny SPZOZ Zespol Szpitali Miejskich W Chorzowie   (Poland)

^e Clinique Sainte Anne   (France)

^f The Catholic University of Korea   (South Korea)

^g HOSPITAL CLÍNICO SAN CARLOS   (Spain)

^h MEDICAL UNIVERSITY OF LODZ   (Poland)

ⁱ Apollo Hospitals Educational and Research Foundation   (India)

^j SINGAPORE GENERAL HOSPITAL   (Singapore)

^k DANA FARBER CANCER INSTITUTE   (United States)

^l MONASH UNIVERSITY   (Australia)

^m HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

ⁿ MOLINETTE HOSPITAL   (Italy)

^o JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^p UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; BISPHOSPHONIC ACID DERIVATIVE; BORTEZOMIB; IMMUNOGLOBULIN A; INTERLEUKIN 6; MELPHALAN; PREDNISONE; SILTUXIMAB;

ADD ON THERAPY; ADULT; AGED; ANEMIA; ARTICLE; BLEEDING; BONE DISEASE; BRONCHOPNEUMONIA; CHROMOSOME 17P; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; GASTROINTESTINAL DISEASE; HERPES ZOSTER; HUMAN; HYPOKALEMIA; INCIDENCE; INFECTION; LEUKOCYTOCLASTIC VASCULITIS; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MULTICENTER STUDY; MULTIPLE MYELOMA; NEURALGIA; NEUTROPENIA; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RADIUS FRACTURE; RESPIRATORY FAILURE; SENSORY NEUROPATHY; SEPTIC SHOCK; SUICIDE; THROMBOCYTOPENIA; VERY ELDERLY;

AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORONIC ACIDS; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 17; DISEASE-FREE SURVIVAL; FEMALE; FOLLOW-UP STUDIES; HUMANS; IMMUNOGLOBULIN A; INTERLEUKIN-6; MALE; MELPHALAN; MIDDLE AGED; MULTIPLE MYELOMA; PREDNISONE; PYRAZINES; SURVIVAL RATE;

EID: 84903642514     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2013-12-546374     Document Type: Article

References (31)

1. San Miguel JF, Schlag R, Khuageva NK, et al VISTA Trial Investigators. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359(9): 906-917.
2. San Miguel JF, Schlag R, Khuageva N, et al. Phase 3 VISTA trial, after 5 years' follow-up, demonstrates a persistent significant overall survival benefit with bortezomib-melphalanprednisone versus melphalan-prednisone, and no increased risk of second primary malignancies, in patients with previously untreated multiple myeloma. J Clin Oncol. 2013; 31(25):448-455.
3. Janssen-Cilag International N.V. Velcade (bortezomib) summary of product characteristics. http://www.ema.europa.eu/docs/en-GB/ document-library/EPAR--- Product-Information/ human/000539/WC500048471.pdf. Accessed December 20, 2013.
4. Millennium Pharmaceuticals, Inc. Velcade United States package insert. http://www.accessdata. fda.gov/drugsatfda-docs/label/2012/021602s031s032lbl.pdf. Accessed December 20, 2013.
5. Sonneveld P, Goldschmidt H, Rosiñol L, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013;31(26):3279-3287.
6. Rawstron AC, Fenton JA, Ashcroft J, et al. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells. Blood. 2000;96(12):3880-3886.
7. Pelliniemi TT, Irjala K, Mattila K, et al Finnish Leukemia Group. Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Blood. 1995;85(3):765-771.
8. Kishimoto T. The biology of interleukin-6. Blood. 1989;74(1):1-10. (Pubitemid 19187402)
9. Chauhan D, Uchiyama H, Akbarali Y, et al. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood. 1996;87(3):1104-1112. (Pubitemid 26043538)
10. Hata H, Xiao H, Petrucci MT, Woodliff J, Chang R, Epstein J. Interleukin-6 gene expression in multiple myeloma: a characteristic of immature tumor cells. Blood. 1993;81(12):3357-3364. (Pubitemid 23172921)
11. Hilbert DM, Kopf M, Mock BA, Köhler G, Rudikoff S. Interleukin 6 is essential for in vivo development of B lineage neoplasms. J Exp Med. 1995;182(1):243-248.
12. Trikha M, Corringham R, Klein B, Rossi JF. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res. 2003;9(13): 4653-4665. (Pubitemid 37323267)
13. Voorhees PM, Chen Q, Kuhn DJ, et al. Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma. Clin Cancer Res. 2007;13(21):6469-6478. (Pubitemid 350075037)
14. Voorhees PM, Chen Q, Small GW, et al. Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death. Br J Haematol. 2009;145(4):481-490.
15. Hunsucker SA, Magarotto V, Kuhn DJ, et al. Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma. Br J Haematol. 2011;152(5):579-592.
16. van Rhee F, Fayad L, Voorhees P, et al. Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease. J Clin Oncol. 2010;28(23):3701-3708.
17. Kurzrock R, Voorhees PM, Casper C, et al. A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease. Clin Cancer Res. 2013; 19(13):3659-3670.
18. Wong R, Casper C, Munshi N, et al. A multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with multicentric Castleman's disease [abstract]. Blood. 2013;122(21):505.
19. Voorhees PM, Manges RF, Sonneveld P, et al. A phase 2 multicentre study of siltuximab, an anti-interleukin- 6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Br J Haematol. 2013;161(3):357-366.
20. Orlowski R, Gercheva L, Williams C, et al. Phase 2, randomized, double blind, placebo controlled study comparing siltuximab1 bortezomib vs. bortezomib alone in pts with relapsed/refractory multiple myeloma [abstract]. J Clin Oncol. 2012; 30(15 suppl): Abstract 8018.
21. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol. 2011;12(5):431-440.
22. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-3420.
23. Bladé J, Samson D, Reece D, et al Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by highdose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102(5): 1115-1123. (Pubitemid 28435189)
24. Rajkumar SV, Harousseau J-L, Durie B, et al; International Myeloma Workshop Consensus Panel 1. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011;117(18):4691-4695.
25. Simon R, Wittes RE, Ellenberg SS. Randomized phase II clinical trials. Cancer Treat Rep. 1985; 69(12):1375-1381. (Pubitemid 16163075)
26. Angevin E, Elez E, Cohen S, et al. Phase 1/2, 2-part, open-label, multiple-dose, dose-escalation study of siltuximab in patients with solid tumors [abstract]. J Clin Oncol. 2012;30(15 suppl): Abstract 2583.
27. Hideshima T, Chauhan D, Hayashi T, et al. Proteasome inhibitor PS-341 abrogates IL-6 triggered signaling cascades via caspase-dependent downregulation of gp130 in multiple myeloma. Oncogene. 2003;22(52):8386-8393. (Pubitemid 37523890)
28. Munshi N, Anderson K, Bersagel L, et al. Guidelines for risk stratification in multiple myeloma: report of the International Myeloma Worskhop Consensus Panel 2. Blood. 2011; 117(18):4696-4700.
29. Van Rhee F, Casper C, Voorhees P, et al. An open-label, phase 2, multicenter study of the safety of long-term treatment with siltuximab (an anti-interleukin-6 monoclonal antibody) in patients with multicentric Castleman's disease [abstract]. Blood. 2013;122(21):1806.
30. Lust JA, Lacy MQ, Zeldenrust SR, et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1beta-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. 2009; 84(2):114-122.
31. Rajkumar SV, Lacy MQ, Kyle RA. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. Blood Rev. 2007; 21(5):255-265. (Pubitemid 47212600)