Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial

Blood Cancer Journal

Volumn 6, Issue 2, 2016, Pages

  Shah, J J ^a   Feng, L ^a   Thomas, S K ^a   Berkova, Z ^a   Weber, D M ^a   Wang, M ^a   Qazilbash, M H ^a   Champlin, R E ^a   Mendoza, T R ^a   Cleeland, C ^a   Orlowski, R Z ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; BORTEZOMIB; DEXAMETHASONE; LENALIDOMIDE; MONOCLONAL ANTIBODY; SILTUXIMAB; THALIDOMIDE;

AGED; ANALOGS AND DERIVATIVES; CANCER STAGING; CHROMOSOME ABERRATION; CLINICAL TRIAL; DISEASE COURSE; FEMALE; GENETICS; HUMAN; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MULTICENTER STUDY; MULTIPLE MYELOMA; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; QUALITY OF LIFE; TREATMENT OUTCOME;

AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BORTEZOMIB; CHROMOSOME ABERRATIONS; DEXAMETHASONE; DISEASE PROGRESSION; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM STAGING; QUALITY OF LIFE; THALIDOMIDE; TREATMENT OUTCOME;

EID: 85018193822     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/BCJ.2016.4     Document Type: Article

References (28)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9–29.
2. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 2009; 27: 2758–2765.
3. Durie BG. New approaches to treatment for multiple myeloma: durable remission and quality of life as primary goals. Clin Lymphoma Myeloma 2005; 6: 181–190.
4. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21–33.
5. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Fanourakis G, Gu X et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci USA 2002; 99: 14374–14379.
6. Hideshima T, Richardson P, Chauhan D, Palombella VJ, Elliott PJ, Adams J et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and over-comes drug resistance in human multiple myeloma cells. Cancer Res 2001; 61: 3071–3076.
7. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002; 99: 4525–4530.
8. Anderson KC, Jagannath S, Jakubowiak A, Lonial S, Raje N, Alsina M et al. Lenalidomide, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma (MM): Encouraging outcomes and tolerability in a phase II study. J Clin Oncol 2009; 27: 8536.
9. Laubach JP, Schlossman RL, Mitsiades CS, Anderson KC, Richardson PG. Thalidomide Cenalidomide and bortezomib in the management of newly diagnosed multiple myeloma. Expert Rev Hematol 2011; 4: 51–60.
10. Jimenez-Zepeda VH, Reece DE, Trudel S, Chen C, Tiedemann R, Kukreti V. Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for heavily pretreated relapsed or refractory multiple myeloma. Leuk Lymphoma 2013; 54: 555–560.
11. Rawstron AC, Fenton JA, Ashcroft J, English A, Jones RA, Richards SJ et al. The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells. Blood 2000; 96: 3880–3886.
12. Tanabe O, Kawano M, Tanaka H, Iwato K, Asaoku H, Ishikawa H et al. BSF-2/IL-6 does not augment Ig secretion but stimulates proliferation in myeloma cells. Am J Hematol 1989; 31: 258–262.
13. Pelliniemi TT, Irjala K, Mattila K, Pulkki K, Rajamaki A, Tienhaara et al. Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Finnish Leukemia Group. Blood 1995; 85: 765–771.
14. Bataille R, Barlogie B, Lu ZY, Rossi JF, Lavabre-Bertrand T, Beck T et al. Biologic effects of anti-interleukin-6 murine monoclonal antibody in advanced multiple myeloma. Blood 1995; 86: 685–691.
15. Lichtenstein A, Tu Y, Fady C, Vescio R, Berenson J. Interleukin-6 inhibits apoptosis of malignant plasma cells. Cell Immunol 1995; 162: 248–255.
16. Hardin J, MacLeod S, Grigorieva I, Chang R, Barlogie B, Xiao H et al. Interleukin-6 prevents dexamethasone-induced myeloma cell death. Blood 1994; 84: 3063–3070.
17. Chauhan D, Kharbanda S, Ogata A, Urashima M, Teoh G, Robertson M et al. Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood 1997; 89: 227–234.
18. Rossi JF, Lu ZY, Jourdan M, Klein B. Interleukin-6 as a therapeutic target. Clin Cancer Res 2015; 21: 1248–1257.
19. Durie BG, Kyle RA, Belch A, Bensinger W, Blade J, Boccadoro M et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation. Hematol J 2003; 4: 379–398.
20. Storer BE. Design and analysis of phase I clinical trials. Biometrics 1989; 45: 925–937.
21. Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115–1123.
22. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014; 15: e538–e548.
23. Jones D, Vichaya EG, Wang XS, Williams LA, Shah ND, Thomas SK et al. Validation of the M. D. Anderson Symptom Inventory multiple myeloma module. J Hematol Oncol 2013; 6: 13.
24. Kurzrock R, Voorhees PM, Casper C, Furman RR, Fayad L, Lonial S 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: 3659–3670.
25. Voorhees PM, Manges RF, Sonneveld P, Jagannath S, Somlo G, Krishnan 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: 357–366.
26. San-Miguel J, Blade J, Shpilberg O, Grosicki S, Maloisel F, Min CK et al. Phase 2 randomized study of bortezomib-melphalan-prednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood 2014; 123: 4136–4142.
27. Orlowski RZ, Gercheva L, Williams C, Sutherland H, Robak T, Masszi T et al. A phase 2, randomized, double-blind, placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma. Am J Hematol 2015; 90: 42–49.
28. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010; 116: 679–686.