Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma

Blood

Volumn 128, Issue 3, 2016, Pages 384-394

  Krejcik, Jakub ^a,b   Casneuf, Tineke ^c   Nijhof, Inger S ^a   Verbist, Bie ^c   Bald, Jaime ^c   Plesner, Torben ^b   Syed, Khaja ^c   Liu, Kevin ^d   Van De Donk, Niels W C J ^a   Weiss, Brendan M ^e   Ahmadi, Tahamtan ^c   Lokhorst, Henk M ^a   Mutis, Tuna ^a   Sasser, A Kate ^c  

^a VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^c JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^d LLC   (United States)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD38 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; DARATUMUMAB; CD38 PROTEIN, HUMAN; MEMBRANE PROTEIN; MONOCLONAL ANTIBODY; TUMOR PROTEIN;

ALLOIMMUNITY; ARTICLE; B LYMPHOCYTE; CANCER RECURRENCE; CELL EXPANSION; CLONAL VARIATION; CYTOTOXIC T LYMPHOCYTE; DRUG MECHANISM; DRUG SENSITIVITY; DRUG TARGETING; HELPER CELL; HUMAN; HUMAN CELL; IMMUNOREGULATION; IMMUNOSUPPRESSIVE TREATMENT; IN VITRO STUDY; LYMPHOCYTE COUNT; LYMPHOCYTE FUNCTION; MEMORY T LYMPHOCYTE; MONOTHERAPY; MULTIPLE MYELOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; SUPPRESSOR CELL; ADOLESCENT; ADULT; AGED; BLOOD; CD4 CD8 RATIO; CD8+ T LYMPHOCYTE; CHILD; CLINICAL TRIAL; FEMALE; IMMUNOLOGY; INFANT; MALE; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRESCHOOL CHILD; VERY ELDERLY;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIGENS, CD38; CD4-CD8 RATIO; CD8-POSITIVE T-LYMPHOCYTES; CHILD; CHILD, PRESCHOOL; FEMALE; HUMANS; INFANT; MALE; MEMBRANE GLYCOPROTEINS; MIDDLE AGED; MULTIPLE MYELOMA; NEOPLASM PROTEINS; T-LYMPHOCYTES, REGULATORY;

EID: 84979519854     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2015-12-687749     Document Type: Article

References (36)

1. Harousseau JL. Ten years of improvement in the management of multiple myeloma: 2000-2010. Clin Lymphoma Myeloma Leuk. 2010;10(6):424-442.
2. Kastritis E, Zervas K, Symeonidis A, et al. Improved survival of patients with multiple myeloma after the introduction of novel agents and the applicability of the International Staging System (ISS): an analysis of the Greek Myeloma Study Group (GMSG). Leukemia. 2009;23(6):1152-1157.
3. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516-2520.
4. Kumar SK, Lee JH, Lahuerta JJ, et al; International Myeloma Working Group. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012;26(1):149-157.
5. Dosani T, Carlsten M, Maric I, Landgren O. The cellular immune system in myelomagenesis: NK cells and T cells in the development of myeloma [corrected] and their uses in immunotherapies. Blood Cancer J. 2015;5:e306.
6. Ray A, Das DS, Song Y, et al. Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells, natural killer cells and multiple myeloma cells. Leukemia. 2015;29(6):1441-1444.
7. Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204(6):1257-1265.
8. Zarek PE, Huang CT, Lutz ER, et al. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood. 2008;111(1):251-259.
9. Binsfeld M, Fostier K, Muller J, et al. Cellular immunotherapy in multiple myeloma: lessons from preclinical models. Biochim Biophys Acta. 2014;1846(2):392-404.
10. Feyler S, von Lilienfeld-Toal M, Jarmin S, et al. CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(-)CD8(-) alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden. Br J Haematol. 2009;144(5):686-695.
11. Roeven MW, Hobo W, Schaap N, Dolstra H. Immunotherapeutic approaches to treat multiple myeloma. Hum Vaccin Immunother. 2014;10(4):896-910.
12. Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121(4):482-488.
13. Santonocito AM, Consoli U, Bagnato S, et al. Flow cytometric detection of aneuploid CD38(++) plasmacells and CD19(+) B-lymphocytes in bone marrow, peripheral blood and PBSC harvest in multiple myeloma patients. Leuk Res. 2004;28(5):469-477.
14. Karakasheva TA, Waldron TJ, Eruslanov E, et al. CD38-expressing myeloid-derived suppressor cells promote tumor growth in a murine model of esophageal cancer. Cancer Res. 2015;75(19):4074-4085.
15. Flores-Borja F, Bosma A, Ng D, et al. CD19+ CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013;5(173):173ra23.
16. de Weers M, Tai YT, van der Veer MS, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186(3):1840-1848.
17. Overdijk MB, Verploegen S, Bögels M, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7(2):311-321.
18. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373(13):1207-1219.
19. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387(10027):1551-1560.
20. McKeage K. Daratumumab: first global approval. Drugs. 2016;76(2):275-281.
21. Rajkumar SV, Harousseau JL, 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.
22. van de Donk NW, Moreau P, Plesner T, et al. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma. Blood. 2016;127(6):681-695.
23. Görgün GT, Whitehill G, Anderson JL, et al. Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood. 2013;121(15):2975-2987.
24. Robins H, Desmarais C, Matthis J, et al. Ultrasensitive detection of rare T cell clones. J Immunol Methods. 2012;375(1-2):14-19.
25. Weisberg S. Applied Linear Regression. Hoboken, NJ: Wiley; 2014.
26. Bates D, Maechler M, Bolker BM, Walker S. Fitting linear mixed-effects models using Ime4. J Stat Softw. 2015;67(1).
27. Royston P. Remark AS R94: A remark on Algorithm AS 181: the W test for normality. J Royal Stat Society, Series C (Applied Stats). 1995;44(4):547-551.
28. Hollander M, Wolfe DA. Nonparametric Statistical Methods. New York: John Wiley & Sons; 1973:27-75.
29. Kotsakis A, Harasymczuk M, Schilling B, Georgoulias V, Argiris A, Whiteside TL. Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samples. J Immunol Methods. 2012;381(1-2):14-22.
30. Qu P, Wang LZ, Lin PC. Expansion and functions of myeloid-derived suppressor cell in the tumor microenvironment [published online ahead of print October 28, 2015]. Cancer Lett. doi:10.1016/j.canlet.2015.10.022.
31. 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.
32. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455-2465.
33. Garon EB, Rizvi NA, Hui R, et al; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028.
34. 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.
35. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.
36. Lee CS, Cragg M, Glennie M, Johnson P. Novel antibodies targeting immune regulatory checkpoints for cancer therapy. Br J Clin Pharmacol. 2013;76(2):233-247.