A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma

Clinical Cancer Research

Volumn 21, Issue 18, 2015, Pages 4055-4061

  Benson, Don M ^a   Cohen, Adam D ^b   Jagannath, Sundar ^c   Munshi, Nikhil C ^d,e   Spitzer, Gary ^f   Hofmeister, Craig C ^a   Efebera, Yvonne A ^a   Andre, Pascale ^g   Zerbib, Robert ^g   Caligiuri, Michael A ^a  

^a OHIO STATE UNIVERSITY   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d DANA FARBER CANCER INSTITUTE   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f St Francis Health System   (United States)

^g INNATE PHARMA   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; IPH 2101; LENALIDOMIDE; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; CORTICOSTEROID; IMMUNOGLOBULIN G; KILLER CELL IMMUNOGLOBULIN LIKE RECEPTOR; LIGAND; MONOCLONAL ANTIBODY; THALIDOMIDE;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ADULT; AGED; ARTICLE; AUTOIMMUNITY; CANCER COMBINATION CHEMOTHERAPY; CANCER RECURRENCE; CANCER SURVIVAL; COHORT ANALYSIS; CONTROLLED STUDY; CYTOKINE RELEASE SYNDROME; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; EYE INFECTION; FEBRILE NEUTROPENIA; FEMALE; HUMAN; HYPOPHOSPHATEMIA; INFUSION RELATED REACTION; LYMPHOCYTE FUNCTION; LYMPHOCYTOPENIA; MALE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELODYSPLASTIC SYNDROME; NATURAL KILLER CELL; NEUTROPENIA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; THROMBOCYTOPENIA; ANALOGS AND DERIVATIVES; CHEMISTRY; CLINICAL TRIAL; CYTOLOGY; DRUG RESISTANCE; IMMUNE SYSTEM; IMMUNOTHERAPY; MIDDLE AGED; MULTICENTER STUDY; PATHOLOGY; TREATMENT OUTCOME; TUMOR RECURRENCE;

ADRENAL CORTEX HORMONES; ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; COHORT STUDIES; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; IMMUNE SYSTEM; IMMUNOGLOBULIN G; IMMUNOTHERAPY; KILLER CELLS, NATURAL; LIGANDS; MALE; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM RECURRENCE, LOCAL; RECEPTORS, KIR; THALIDOMIDE; TREATMENT OUTCOME;

EID: 84942933304     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-0304     Document Type: Article

References (32)

1. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy M.Q., Hayman SR, Buadi FK, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008; 111: 2516-20.
2. Davies FE, Raje N, Hideshima T., Lentzsch S, Young G, Tai Y.T., et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98: 210-6.
3. Hayashi T, Hideshima T, Akiyama M., Podar K, Yasui H, Raje N., et al. Molecular mechanisms whereby immunomodulatory drugs activate natural killer cells: clinical application. Br J Haematol 2005; 128: 192-203.
4. Zhu D, Corral LG, Fleming Y.W., Stein B. Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solidtumor cells through NK cell activation. Cancer Immunol Immunother 2008; 57: 1849-59.
5. Carbone E, Neri P, Mesuraca M., Fulciniti MT, Otsuki T, Pende D, et al HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood 2005; 105: 251-8.
6. Sawanobori M, Suzuki K, Nakagawa Y., Inoue Y, Utsuyama M, Hirokawa K. Natural killer cell frequency and serum cytokine levels in monoclonal gammopathies: correlation of bone marrow granular lymphocytes to prognosis. Acta Haematol 1997; 98: 150-4.
7. Osterborg A, Nilsson B, Bjorkholm M., Holm G, Mellstedt H. Natural killer cell activity in monoclonal gammopathies: relation to disease activity. Eur J Haematol 1990; 45: 153
8. Gonzalez M, San Miguel JF, Gascon A, Moro MJ, Hernandez J.M., Ortega F., et al. Increased expression of natural-killer-associated and activation antigens in multiple myeloma. Am J Hematol 1992; 39: 84-9.
9. Garcia-Sanz R., Gonzalez M, Orfao A., Moro MJ, Hernandez JM, Borrego D, et al Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications. Br J Haematol 1996; 93: 81-8.
10. Frassanito MA, Silvestris F, Cafforio P., Silvestris N, Dammacco F. IgG M-components in active myeloma patients induce a down-regulation of natural killer cell activity. Int J Clin Lab Res 1997; 27: 48-54.
11. Nielsen H, Nielsen HJ, Tvede N, Klarlund K., Mansa B, Moesgaard F, et al Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors. APMIS 1991; 99: 340-6.
12. Beyer M, Kockanek M, Giese T., Endl E, Weihrauch MR, Knolle P.A., et al. In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood 2006; 107: 3940-9.
13. Tinofer I, Marschitz I, Henn T., Egle A, Greil R. Expression of a functional interleukin-15 receptor and autocrine production of interleukin-15 as mechanisms of tumor propagation in multiple myeloma. Blood 2000; 95: 610-8.
14. Hsu AK, Quach H, Tai T., Prince HM, Harrison SJ, Trapani JA, Smyth M.J., Neeson P., Ritchie DS. The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy. Blood 2011; 117: 1605-13.
15. Carter CR, Feyler S, Smalle N., Scott GB, Parrish C, Cullen K, et al Effect of combined dexamethasone/lenalidomide therapy on NK cell-receptor levels in myeloma patients. Blood 2011; 118: 6465-6.
16. Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomized controlled trial. Lancet Oncol 2010; 11: 29-37.
17. Mitsiades CS. How "immunomodulatory" are IMIDs? Blood 2011; 117:1440-1.
18. Romagne F, Andre P, Spee P., Zahn S, Anfossi N, Gauthier L., et al. Preclinical characterization of 1-7F9, a novel anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood 2009; 114:2667-77.
19. Ruggeri L, Capanni M, Urbani E., Perruccio K, Shlomchik WD, Tosti A, et al Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295: 2097-2100.
20. Benson DM J.r., Hofmeister CC, Padmanabhan S, Suvannasankha A., Jagannath S, Abonour R, et al A phase I trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood 2012; 120: 4324-33.
21. Benson DM J.r., Bakan CE, Zhang S, Collins S.M., Liang J., Srivastava S, et al. IPH2101, a novel anti-inhibitory KIR antibody, and lendalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 2011; 118: 6387-91.
22. Godfrey J, Benson DM Jr. The role of natural killer cells in immunity against multiple myeloma. Leuk Lymphoma 2012; 53: 1666-76.
23. Kroger N, Shaw B, Iacobelli S., Zabelina T, Peggs K, Shimoni A., et al. Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma. Brit J Haematol 2005; 129: 631-43.
24. Richardson P, Jagannath S, Hussein M., Berenson J, Singhal S, Irwin D., et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009; 114: 772-8.
25. Weber D, Chen C, Niesvizky R., Wang M, Belch A, Stadtmauer E.A., et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. New Eng J Med 2007; 357: 2133-42.
26. Dimopoulos M, Spencer A, Attal M., Prince HM, Harousseau JL, Dmoszynska A, et al Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. New Eng J Med 2007; 357: 2123-32.
27. Allegra A, Penna G, Alonci A., Russo S, Greve B, Innao V., et al. Monoclonal antibodies: potential new therapeutic treatment against multiple myeloma. Eur J Haematol 2013; 90: 441-68.
28. Chu J, Deng Y, Benson D.M., He S., Hughes T, Zhang J, et al CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo anti-tumor activity against human multiple myeloma. Leukemia 2014; 28: 917-27.
29. Wang L, Jin N, Schmitt A., Greiner J, Malcherek G, Hundemer M., et al. Tcell-based targeted immunotherapies for patientswith multiple myeloma. Int J Cancer 2015; 136: 1751-68.
30. Benson DM, Byrd JC CS-1 directed monoclonal antibody therapy for multiple myeloma. J Clin Oncol 2012; 30: 2013-5.
31. Nijhof IS, Lammerts van Bueren JJ, van Kessel B, Andre P, Morel Y, Lokhorst HM, et al. Daratumumab-mediated lysis of primary multiple myeloma cells is enhanced in combination with the human anti-KIR antibody IPH2102 and lenalidomide. Haematologica 2015; 100: 263-8.
32. Atanackovic D, Luetkens T, Kroger N. Coinhibitory molecule PD-1 as a potential target for the immunotherapy of multiple myeloma. Leukemia 2014; 28: 993-1000.