The immunotherapy era of myeloma: Monoclonal antibodies, vaccines, and adoptive T-cell therapies

Blood

Volumn 128, Issue 13, 2016, Pages 1679-1687

  Hoyos, Valentina ^a   Borrello, Ivan ^a  

^a JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER TESTIS ANTIGEN; CANCER VACCINE; CD38 ANTIGEN; CD56 ANTIGEN; CELL SURFACE PROTEIN; CHECKPOINT KINASE INHIBITOR; CHIMERIC ANTIGEN RECEPTOR; DARATUMUMAB; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR BASED CELLULAR VACCINE; IDIOTYPE VACCINE; IMMUNOGLOBULIN IDIOTYPE; INTERLEUKIN 6; MONOCLONAL ANTIBODY; SLAMF7 PROTEIN; SYNDECAN 1; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

ADOPTIVE IMMUNOTHERAPY; ALLOGENIC BONE MARROW TRANSPLANTATION; CANCER IMMUNOTHERAPY; CELL THERAPY; HUMAN; LYMPHOCYTIC INFILTRATION; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; IMMUNOTHERAPY; PROCEDURES; TRENDS;

ANTIBODIES, MONOCLONAL; CANCER VACCINES; HUMANS; IMMUNE TOLERANCE; IMMUNOTHERAPY; IMMUNOTHERAPY, ADOPTIVE; MULTIPLE MYELOMA; T-LYMPHOCYTES;

EID: 84990864169     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2016-05-636357     Document Type: Review

References (89)

1. National Cancer Institute statistics. SEER Stat Fact Sheets: Myeloma. Available at: seer.cancer. gov/statfacts/html/mulmy.html. Accessed 10 May 2016.
2. Neri P, Bahlis NJ. Genomic instability in multiple myeloma: mechanisms and therapeutic implications. Expert Opin Biol Ther. 2013; 13(Suppl 1):S69-S82.
3. Pratt G, Goodyear O, Moss P. Immunodeficiency and immunotherapy in multiple myeloma. Br J Haematol. 2007;138(5):563-579.
4. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26): 2443-2454.
5. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4): 311-319.
6. Gill S, June CH. Going viral: chimeric antigen receptor T-cell therapy for hematological malignancies. Immunol Rev. 2015;263(1):68-89.
7. Romano A, Conticello C, Cavalli M, et al. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int. 2014;2014: 198539.
8. Sotomayor EM, Borrello I, Rattis FM, et al. Crosspresentation of tumor antigens by bone marrowderived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood. 2001; 98(4):1070-1077.
9. Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV. Antitumor monoclonal antibodies enhance cross-presentation ofcCellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. J Exp Med. 2002;195(1):125-133.
10. Brown RD, Pope B, Murray A, et al. Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to upregulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-beta1 and interleukin-10. Blood. 2001;98(10):2992-2998.
11. Brimnes MK, Svane IM, Johnsen HE. Impaired functionality and phenotypic profile of dendritic cells from patients with multiple myeloma. Clin Exp Immunol. 2006;144(1):76-84.
12. von Boehmer H. Mechanisms of suppression by suppressor T cells. Nat Immunol. 2005;6(4): 338-344.
13. Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010;127(4):759-767.
14. Giannopoulos K, Kaminska W, Hus I, Dmoszynska A. The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma. Br J Cancer. 2012; 106(3):546-552.
15. Muthu Raja KR, Rihova L, Zahradova L, Klincova M, Penka M, Hajek R. Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma. PLoS One. 2012;7(10):e47077.
16. Shay G, Hazlehurst L, Lynch CC. Dissecting the multiple myeloma-bone microenvironment reveals new therapeutic opportunities. J Mol Med (Berl). 2016;94(1):21-35.
17. Rodriguez PC, Quiceno DG, Zabaleta J, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res. 2004;64(16):5839-5849.
18. Botta C, Gulla A, Correale P, Tagliaferri P, Tassone P. Myeloid-derived suppressor cells in multiple myeloma: pre-clinical research and translational opportunities. Front Oncol. 2014;4: 348.
19. Görgün G, Calabrese E, Soydan E, et al. Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma. Blood. 2010;116(17):3227-3237.
20. Noonan KA, Ghosh N, Rudraraju L, Bui M, Borrello I. Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma. Cancer Immunol Res. 2014;2(8):725-731.
21. Noonan K, Borrello I. The immune microenvironment of myeloma. Cancer Microenviron. 2011;4(3):313-323.
22. Jinushi M, Vanneman M, Munshi NC, et al. MHC class I chain-related protein A antibodies and shedding are associated with the progression of multiple myeloma. Proc Natl Acad Sci USA. 2008; 105(4):1285-1290.
23. Prabhala RH, Pelluru D, Fulciniti M, et al. Elevated IL-17 produced by TH17 cells promotes myeloma cell growth and inhibits immune function in multiple myeloma. Blood. 2010;115(26): 5385-5392.
24. Noonan K, Marchionni L, Anderson J, Pardoll D, Roodman GD, Borrello I. A novel role of IL-17- producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood. 2010; 116(18):3554-3563.
25. Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008; 14(9):2775-2784.
26. Collins SM, Bakan CE, Swartzel GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother. 2013; 62(12):1841-1849.
27. Guo H, Cruz-Munoz ME, Wu N, Robbins M, Veillette A. Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells. Mol Cell Biol. 2015;35(1):41-51.
28. Zonder JA, Mohrbacher AF, Singhal S, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2012;120(3):552-559.
29. Lonial S, Dimopoulos M, Palumbo A, et al; ELOQUENT-2 Investigators. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373(7):621-631.
30. Richardson PG, Jagannath S, Moreau P, et al; 1703 Study Investigators. Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 doseescalation study. Lancet Haematol. 2015;2(12): e516-e527.
31. Palumbo A, Offidani M, Pegourie B, et al. Elotuzumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in patients with relapsed/refractory multiple myeloma: 2-year follow-up. In: Proceedings of the 57th American Society of Hematology; 5-8 December 2015; Orlando, FL. Abstract 510.
32. Usmani SZ, Sexton R, Ailawadhi S, et al. Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211. Blood Cancer J. 2015;5: e334.
33. Malavasi F, Deaglio S, Funaro A, et al. Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology. Physiol Rev. 2008;88(3):841-886.
34. Cockayne DA, Muchamuel T, Grimaldi JC, et al. Mice deficient for the ecto-nicotinamide adenine dinucleotide glycohydrolase CD38 exhibit altered humoral immune responses. Blood. 1998;92(4): 1324-1333.
35. Sandoval-Montes C, Santos-Argumedo L. CD38 is expressed selectively during the activation of a subset of mature T cells with reduced proliferation but improved potential to produce cytokines. J Leukoc Biol. 2005;77(4):513-521.
36. Lonial S, Weiss B, Usmani SZ, et al. Phase II study of daratumumab (DARA) monotherapy in patients with $ 3 lines of prior therapy or double refractory multiple myeloma (MM): 54767414MMY2002 (Sirius). In: Proceedings of the American Society of Clinical Oncology (ASCO) Annual Meeting; 29 May-2 June 2015; Chicago, IL. Abstract LBA8512.
37. Chari A, Lonial S, Suvannasankha A, et al. Open-label, multicenter, phase 1b study of daratumumab in combination with pomalidomide and dexamethasone in patients with at least 2 lines of prior therapy and relapsed or relapsed and refractory multiple myeloma. In: Proceedings from the 57th American Society of Hematology (ASH) Annual Meeting; 5-8 December 2015; Orlando, FL. Abstract 508.
38. Dimopoulos M, Oriol A, Nahi H, et al. An open-label, randomised phase III study of daratumumab, lenalidomide, and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in relapsed or refractory multiple myeloma (RRMM): pollux. In: Proceedings from the European Hematology Association 21st Congress; 9-12 June 2016; Copenhagen, Denmark. Abstract LB2238.
39. Palumbo A, Chanan-Khan AA, Weisel K, et al. Phase III randomized controlled study of daratumumab, bortezomib, and dexamethasone (DVd) versus bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR study. In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract LBA4.
40. Raab MS, Chatterjee M, Goldschmidt H, et al. MOR202 alone and in combination with pomalidomide or lenalidomide in relapsed or refractory multiple myeloma: data from clinically relevant cohorts from a phase I/IIa study. In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract 8012.
41. Vij R, Lendvai N, Martin T, et al. A phase Ib dose escalation trial of isatuximab (SAR650984, anti-CD38 mAb) plus lenalidomide and dexamethasone (Len/Dex) in relapsed/refractory multiple myeloma (RRMM): Interim results from two new dose cohorts. In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract 8009.
42. Richter J, Martin T, Vij R, et al. Updated data from a phase II dose finding trial of single agent isatuximab (SAR650984, anti-CD38 mAb) in relapsed/refractory multiple myeloma (RRMM). In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract 8005.
43. Ikeda H, Hideshima T, Fulciniti M, et al. The monoclonal antibody nBT062 conjugated to cytotoxic Maytansinoids has selective cytotoxicity against CD138-positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res. 2009;15(12): 4028-4037.
44. Heffner L, Jagannath S, Zimmerman T, et al. BT062, an antibody-drug conjugate directed against CD138, given weekly for 3 weeks in each 4 week cycle: safety and further evidence of clinical activity. In: Proceedings from the 54th American Society of Hematology (ASH) Annual Meeting; 8-11 December 2012; Atlanta, GA. Abstract 4042.
45. Kelly K, Chanan-Khan AA, Heffner L, et al. Indatuximab ravtansine (BT062) in combination with lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma: clinical activity in patients already exposed to lenalidomide and bortezomib. In: Proceedings from the 56th American Society of Hematology (ASH) Annual Meeting; 6-9 December 2014; San Francisco, CA. Abstract 4736.
46. Voorhees PM, Manges RF, Sonneveld P, et al. A phase 2 multicentre study of siltuximab, an antiinterleukin- 6 monoclonal antibody, in patients with relapsed or refractory multiple myeloma. Br J Haematol. 2013;161(3):357-366.
47. Orlowski RZ, Gercheva L, Williams C, et al. A phase 2, randomized, double-blind, placebocontrolled 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(1):42-49.
48. San-Miguel J, Bladé J, Shpilberg O, et al. Phase 2 randomized study of bortezomib-melphalanprednisone with or without siltuximab (anti-IL-6) in multiple myeloma. Blood. 2014;123(26):4136-4142.
49. Chanan-Khan AA, Wolf J, Garcia J, et al. Efficacy analysis from phase I study of lorvotuzumab mertansine (IMGN901), used as monotherapy, in patients with heavily pre-treated CD56-positive multiple myeloma: a preliminary efficacy analysis. In: Proceedings from the 52nd American Society of Hematology (ASH) Annual Meeting; 4-7 December 2010; Orlando, FL. Abstract 1962.
50. Berdeja J, Hernandez-Ilizaliturri F, Chanan-Khan AA, et al. Phase I study of lorvotuzumab mertansine (LM, IMGN901) in combination with lenalidomide (Len) and dexamethasone (Dex) in patients with CD56-positive relapsed or relapsed/refractory multiple myeloma (MM). In: Proceedings from the 54th American Society of Hematology (ASH) Annual Meeting; 8-11 December 2012; Atlanta, GA. Abstract 728.
51. Lesokhin AM, Ansell SM, Armand P, et al. Preliminary results of a phase I study of nivolumab (BMS-936558) in patients with relapsed or refractory lymphoid malignancies. In: Proceedings from the 56th American Society of Hematology (ASH) Annual Meeting; 6-9 December 2014; San Francisco, CA. Abstract 291.
52. Mateos MV, Orlowski RZ, Siegel D, et al. Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/refractory multiple myeloma (RRMM): final efficacy and safety analysis. In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract 8010.
53. Badros A, Kocoglu M, Ma N, et al. A phase II study of anti PD-1 antibody pembrolizumab, pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). In: Proceedings from the 57th American Society of Hematology (ASH) Annual Meeting; 5-8 December 2015; Orlando, FL. Abstract 506.
54. Palumbo A, Mateos MV, San-Miguel J, et al. KEYNOTE-185: a randomized, open-label phase 3 study of pembrolizumab in combination with lenalidomide and low-dose dexamethasone in newly diagnosed and treatment-naive multiple myeloma (MM). In: Proceedings from the American Society of Clinical Oncology (ASCO) Annual Meeting; 2-7 June 2016; Chicago, IL. Abstract TPS8069.
55. Weiss S, Bogen B. B-lymphoma cells process and present their endogenous immunoglobulin to major histocompatibility complex-restricted T cells. Proc Natl Acad Sci USA. 1989;86(1):282-286.
56. Yi Q, Dabadghao S, Osterborg A, Bergenbrant S, Holm G. Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells. Blood. 1997;90(5):1960-1967.
57. Thomas AM, Santarsiero LM, Lutz ER, et al. Mesothelin-specific CD8(1) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med. 2004;200(3): 297-306.
58. van Mierlo GJ, Boonman ZF, Dumortier HM, et al. Activation of dendritic cells that cross-present tumor-derived antigen licenses CD81 CTL to cause tumor eradication. J Immunol. 2004; 173(11):6753-6759.
59. Lacy MQ, Mandrekar S, Dispenzieri A, et al. Idiotype-pulsed antigen-presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival. Am J Hematol. 2009;84(12):799-802.
60. Avigan D, Vasir B, Gong J, et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004;10(14): 4699-4708.
61. Rosenblatt J, Glotzbecker B, Mills H, et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother. 2011;34(5):409-418.
62. Condomines M, Hose D, Raynaud P, et al. Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis. J Immunol. 2007;178(5):3307-3315.
63. van Baren N, Brasseur F, Godelaine D, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood. 1999; 94(4):1156-1164.
64. Batchu RB, Moreno AM, Szmania SM, et al. Protein transduction of dendritic cells for NYESO- 1-based immunotherapy of myeloma. Cancer Res. 2005;65(21):10041-10049.
65. Rapoport AP, Aqui NA, Stadtmauer EA, et al. Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells. Clin Cancer Res. 2014;20(5):1355-1365.
66. Borrello I, Noonan K, Huff CA, et al. Allogeneic myeloma GVAX with lenalidomide enhances progression free survival through the generation of tumor specific immunity in patients in near complete remission. In: Proceedings from the 57th American Society of Hematology (ASH) Annual Meeting; 5-8 December 2015; Orlando, FL. Abstract 4238.
67. Noonan K, Rudraraju L, Ferguson A, et al. Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res. 2012; 18(5):1426-1434.
68. Plesner T, Arkenau H, Lokhorst H, et al. Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. In: Proceedings from the 56th American Society of Hematology (ASH) Annual Meeting; 6-9 December 2014; San Francisco, CA. Abstract 84.
69. San-Miguel J, Mateos MV, Shah JJ, et al. Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for relapsed/ refractory multiple myeloma (RRMM). In: Proceedings from the 57th American Society of Hematology (ASH) Annual Meeting; 5-8 December 2015; Orlando, FL. Abstract 505.
70. LeBlanc R, Hideshima T, Catley LP, et al. Immunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood. 2004;103(5): 1787-1790.
71. Neuber B, Herth I, Tolliver C, et al. Lenalidomide enhances antigen-specific activity and decreases CD45RA expression of T cells from patients with multiple myeloma. J Immunol. 2011;187(2): 1047-1056.
72. Levine BL, Bernstein WB, Connors M, et al. Effects of CD28 costimulation on long-term proliferation of CD41 T cells in the absence of exogenous feeder cells. J Immunol. 1997; 159(12):5921-5930.
73. Bruno B, Rotta M, Patriarca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007; 356(11):1110-1120.
74. Armeson KE, Hill EG, Costa LJ. Tandem autologous vs autologous plus reduced intensity allogeneic transplantation in the upfront management of multiple myeloma: meta-analysis of trials with biological assignment. Bone Marrow Transplant. 2013;48(4):562-567.
75. Björkstrand BB, Ljungman P, Svensson H, et al. Allogeneic bone marrow transplantation versus autologous stem cell transplantation in multiple myeloma: a retrospective case-matched study from the European Group for Blood and Marrow Transplantation. Blood. 1996;88(12):4711-4718.
76. Noonan KA, Borrello IM. Marrow infiltrating lymphocytes: their role in adoptive immunotherapy. Cancer J. 2015;21(6):501-505.
77. Noonan K, Matsui W, Serafini P, et al. Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res. 2005;65(5):2026-2034.
78. Noonan KA, Huff CA, Davis J, et al. Adoptive transfer of activated marrowinfiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015;7(288):288ra78.
79. Maus MV, June CH. CARTs on the road for myeloma. Clin Cancer Res. 2014;20(15): 3899-3901.
80. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2): 188-195.
81. Barrett DM, Teachey DT, Grupp SA. Toxicity management for patients receiving novel T-cell engaging therapies. Curr Opin Pediatr. 2014; 26(1):43-49.
82. Garfall AL, Maus MV, Hwang WT, et al. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. N Engl J Med. 2015; 373(11):1040-1047.
83. Matsui W, Wang Q, Barber JP, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008;68(1):190-197.
84. Ali SA, Shi V, Wang M, et al. Remissions of multiple myeloma during a first-in-humans clinical trial of T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor. In: Proceedings from the 57th American Society of Hematology (ASH) Annual Meeting; 5-8 December 2015; Orlando, FL. Abstract LBA-1.
85. Vera J, Savoldo B, Vigouroux S, et al. Tlymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood. 2006;108(12):3890-3897.
86. Chu J, He S, Deng Y, et al. Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells. Clin Cancer Res. 2014;20(15):3989-4000.
87. Jiang H, Zhang W, Shang P, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8(2):297-310.
88. Drent E, Groen RW, Noort WA, et al. Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. Haematologica. 2016;101(5):616-625.
89. Rapoport AP, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21(8):914-921.