A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome

American Journal of Hematology

Volumn 89, Issue 9, 2014, Pages

  Garcia Manero, Guillermo ^a   Gartenberg, Gary ^b   Steensma, David P ^c   Schipperus, Martin R ^d   Breems, Dimitri A ^e   de Paz, Raquel ^f   Valcárcel, David ^g   Kranenburg, Britte ^h   Reddy, Manjula ⁱ   Komrokji, Rami S ^j  

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

^b JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d HAGA HOSPITAL   (Netherlands)

^e Hospital Network Antwerp   (Belgium)

^f HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

^g UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^h Janssen Biologics   (Netherlands)

ⁱ JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^j H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

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Author keywords

[No Author keywords available]

Indexed keywords

ANTIANEMIC AGENT; BETA 2 MICROGLOBULIN; BONE MORPHOGENETIC PROTEIN 6; C REACTIVE PROTEIN; CYCLOSPORIN; ERYTHROPOIETIN; FERRITIN; HEMOGLOBIN; HEPCIDIN; INTERLEUKIN 6; IRON CHELATING AGENT; LENALIDOMIDE; LEPTIN; PLACEBO; SILTUXIMAB; THYMOCYTE ANTIBODY; TUMOR NECROSIS FACTOR ALPHA;

ACUTE HEART INFARCTION; ADULT; AGED; ANEMIA; ARTICLE; BACKACHE; BACTEREMIA; BONE MARROW; CELLULITIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ARTICLE; COMPARATIVE EFFECTIVENESS; CONGESTIVE HEART FAILURE; CONTROLLED STUDY; COUGHING; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG WITHDRAWAL; ERYTHROCYTE TRANSFUSION; FEMALE; FERRITIN BLOOD LEVEL; HEART PALPITATION; HEART VENTRICLE FIBRILLATION; HEMOGLOBIN BLOOD LEVEL; HEMOGLOBIN DETERMINATION; HEMORRHOID HEMORRHAGE; HUMAN; INFESTATION; INFUSION RELATED REACTION; INTERMEDIATE RISK PATIENT; INTERNATIONAL PROGNOSTIC SCORING SYSTEM; LIMB PAIN; LIVER DYSFUNCTION; LOW RISK PATIENT; MALE; MAXIMUM PLASMA CONCENTRATION; MEDICAL CARE; MULTICENTER STUDY; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; PARALYSIS; PERIPHERAL EDEMA; PHARMACODYNAMICS; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; SEPSIS; SEPTIC SHOCK; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TREATMENT DURATION; UPPER RESPIRATORY TRACT INFECTION;

AGED; AGED, 80 AND OVER; ANEMIA, REFRACTORY; ANTIBODIES, MONOCLONAL; COMBINED MODALITY THERAPY; DOUBLE-BLIND METHOD; EARLY TERMINATION OF CLINICAL TRIALS; ERYTHROCYTE TRANSFUSION; FEMALE; HEMOGLOBINS; HUMANS; INTERLEUKIN-6; MALE; MEDICAL FUTILITY; MIDDLE AGED; MYELODYSPLASTIC SYNDROMES; PATIENT CARE;

EID: 84906075354     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23780     Document Type: Article

References (24)

1. Zeidan AM, Linhares Y, Gore SD. Current therapy of myelodysplastic syndromes. Blood Rev 2013;27:243-259.
2. Hsu HC, Lee YM, Tsai WH, et al. Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome. Oncology 2002;63:64-69.
3. Flores-Figueroa E, Gutierrez-Espindola G, Montesinos JJ, et al. In vitro characterization of hematopoietic microenvironment cells from patients with myelodysplastic syndrome. Leuk Res 2002;26:677-686.
4. Manakova TE, Tsvetaeva NV, Levina AA, et al. In vivo production of cytokines by bone marrow stromal cells and macrophages from patients with myelodysplastic syndrome. Bull Exp Biol Med 2001;132:633-636.
5. Verma A, List AF. Cytokine targets in the treatment of myelodysplastic syndromes. Curr Hematol Rep 2005;4:429-435.
6. Allampallam K, Shetty V, Mundle S, et al. Biological significance of proliferation, apoptosis, cytokines, and monocyte/macrophage cells in bone marrow biopsies of 145 patients with myelodysplastic syndrome. Int J Hematol 2002;75:289-297.
7. Allampallam K, Shetty V, Hussaini S, et al. Measurement of mRNA expression for a variety of cytokines and its receptors in bone marrows of patients with myelodysplastic syndromes. Anticancer Res 1999;19:5323-5328.
8. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004;113:1271-1276.
9. Schipperus MR, Sonneveld P, Lindemans J, et al. Interleukin-6 and interleukin-1 enhancement of GM-CSF-dependent proliferation of haematopoietic progenitor cells in myelodysplastic syndromes. Br J Haematol 1991;77:515-522.
10. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-2093.
11. Cuijpers ML, Raymakers RA, Mackenzie MA, et al. Recent advances in the understanding of iron overload in sideroblastic myelodysplastic syndrome. Br J Haematol 2010;149:322-333.
12. Tehranchi R, Invernizzi R, Grandien A, et al. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood 2005;106:247-253.
13. Komrokji RS, Corrales-Yepez M, Kharfan-Dabaja MA, et al. Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes. Am J Hematol 2012;87:1006-1009.
14. 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;28:3701-3708.
15. Schipperus M, Cornfeld M, Rijnbeek B, et al. CNTO328 (Anti-IL-6 mAb) treatment and hemoglobin (Hb) levels in renal cell cancer. J Clin Oncol 2009;27. Abstract e20648.
16. Dorff TB, Goldman B, Pinski JK, et al. Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer. Clin Cancer Res 2010;16:3028-3034.
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;19:3659-3670.
18. Stone K, Woods E, Szmania SM, et al. Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman Disease and is associated with increased soluble interleukin-6 receptor levels. PLoS One 2013;8:e54610.
19. Angevin E, Tabernero J, Elez ME, et al. A phase 1/2, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res 2014;20:2192-2204.
20. Legouffe E, Rodriguez C, Picot MC, et al. C-reactive protein serum level is a valuable and simple prognostic marker in non Hodgkin's lymphoma. Leuk Lymphoma 1998;31:351-357.
21. 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;9:4653-4665.
22. Andriopoulos B Jr, Corradini E, Xia Y, et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 2009;41:482-487.
23. Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 2002;110:1037-1044.
24. San Miguel J, Blade J, Shpilberg O, et al. Randomized, open label, phase 2 study of siltuximab (an anti-IL-6 mAb) and bortezomib-melphalan-prednisone versus bortezomib-melphalan-prednisone in patients with newly diagnosed multiple myeloma. Blood, [Epub ahead of print.].