The mechanism of action of the anti-CD38 monoclonal antibody isatuximab in multiple myeloma

Clinical Cancer Research

Volumn 25, Issue 10, 2019, Pages 3176-3187

  Moreno, Laura ^a   Perez, Cristina ^a   Zabaleta, Aintzane ^a   Manrique, Irene ^a   Alignani, Diego ^a   Ajona, Daniel ^a,b,c   Blanco, Laura ^a   Lasa, Marta ^a   Maiso, Patricia ^a   Rodriguez, Idoia ^a   Garate, Sonia ^a   Jelinek, Tomas ^a   Segura, Victor ^a   Moreno, Cristina ^a   Merino, Juana ^a   Rodriguez Otero, Paula ^a   Panizo, Carlos ^a   Prosper, Felipe ^a   San Miguel, Jesus F ^a   Paiva, Bruno ^a  

^a UNIVERSITY CLINIC OF NAVARRA   (Spain)

^b UNIVERSITY OF NAVARRA   (Spain)

^c UNIVERSITY OF NAVARRA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

ADP RIBOSYL CYCLASE/CYCLIC ADP RIBOSE HYDROLASE 1; BORTEZOMIB; COMPLEMENT COMPONENT C3; DEXAMETHASONE; ISATUXIMAB; LENALIDOMIDE; DARATUMUMAB; MONOCLONAL ANTIBODY;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY DEPENDENT CELLULAR PHAGOCYTOSIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CELL PHAGOCYTOSIS; CELL PROLIFERATION; CELL SURFACE; CLINICAL ARTICLE; COMPLEMENT ACTIVATION; COMPLEMENT DEPENDENT CYTOTOXICITY; CONTROLLED STUDY; DRUG MECHANISM; DRUG POTENTIATION; DRUG SENSITIZATION; EX VIVO STUDY; HUMAN; HUMAN CELL; HUMAN TISSUE; INTERNALIZATION; LYMPHOCYTE ACTIVATION; LYMPHOCYTE DEPLETION; MULTIPLE MYELOMA; MULTIPLE MYELOMA CELL LINE; NATURAL KILLER CELL; PLASMA CELL; PRE B LYMPHOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SECRETION; SIGNAL TRANSDUCTION; IMMUNOLOGY;

ADP-RIBOSYL CYCLASE 1; ANTIBODIES, MONOCLONAL; HUMANS; MULTIPLE MYELOMA;

EID: 85065785802     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-18-1597     Document Type: Article

References (45)

1. Bachireddy P, Burkhardt UE, Rajasagi M, Wu CJ. Haematological malignancies: at the forefront of immunotherapeutic innovation. Nat Rev Cancer 2015;15:201–15.
2. Rodriguez-Otero P, Paiva B, Engelhardt M, Prosper F, San Miguel JF. Is immunotherapy here to stay in multiple myeloma? Haematologica 2017; 102:423–432.
3. Weiner GJ. Building better monoclonal antibody-based therapeutics. Nat Rev Cancer 2015;15:361–70.
4. Tutt AL, French RR, Illidge TM, Honeychurch J, McBride HM, Penfold CA, et al. Monoclonal antibody therapy of B cell lymphoma: signaling activity on tumor cells appears more important than recruitment of effectors. J Immunol 1998;161:3176–85.
5. Taylor RP. Of mice and mechanisms: identifying the role of complement in monoclonal antibody-based immunotherapy. Haematologica 2006;91:146a.
6. Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch J V. Fc receptors are required in passive and active immunity to melanoma. Proc Natl Acad Sci U S A 1998;95:652–6.
7. Chen J, Zhong M-C, Guo H, Davidson D, Mishel S, Lu Y, et al. SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin. Nature 2017;544:493–7.
8. Arana P, Paiva B, Cedena M-T, Puig N, Cordon L, Vidriales M-B, et al. Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials. Leukemia 2018;32:971–8.
9. Flores-Montero J, Flores LS, Paiva B, Puig N, Garcia-Sanchez O, Bottcher S, et al. Next generation flow (NGF) for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia 2017;31:2094–103.
10. Overdijk MB, Jansen JH, Nederend M, Lammerts van Bueren JJ, Groen RW, Parren PW, et al. The Therapeutic CD38 monoclonal antibody daratumumab induces programmed cell death via fcgamma receptor-mediated cross-linking. J Immunol 2016;197:807–13.
11. de Weers M, Tai Y-T, van der Veer MS, Bakker JM, Vink T, Jacobs DCH, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol 2011;186:1840–8.
12. Overdijk MB, Verploegen S, Bogels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, et al. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs 2015;7:311–21.
13. Nijhof IS, Groen RW, Noort WA, van Kessel B, de Jong-Korlaar R, Bakker J, et al. Preclinical evidence for the therapeutic potential of CD38-targeted immuno-chemotherapy in multiple myeloma patients refractory to lenalidomide and bortezomib. Clin Cancer Res 2015;21:2802–10.
14. þ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood 2016;128: 384–94.
15. Krejcik J, Frerichs KA, Nijhof IS, van Kessel B, van Velzen J, Bloem AC, et al. Monocytes and granulocytes reduce CD38 expression levels on myeloma cells in patients treated with daratumumab. Clin Cancer Res 2017;23: 7498–511.
16. Kastritis E, Dimopoulos MA. Daratumumab combinations: what can we learn? Blood 2017;130:957–8.
17. 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.
18. Chiu C, Casneuf T, Axel A, Lysaght A, Bald J, Khokhar NZ, et al. Daratumumab in combination with lenalidomide plus dexamethasone induces clonality increase and T-cell expansion: results from a phase 3 randomized study (POLLUX). Blood 2016;128:4531.
19. Plesner T, Arkenau H-T, Gimsing P, Krejcik J, Lemech C, Minnema MC, et al. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood 2016;128:1821–8.
20. Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016;375:1319–31.
21. Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017;130:974–81.
22. Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood 2017;129:3294–303.
23. þ hematologic malignancies. Clin Cancer Res 2014;20: 4574–83.
24. Jiang H, Acharya C, An G, Zhong M, Feng X, Wang L, et al. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide. Leukemia 2016;30:399–408.
25. Horenstein AL, Chillemi A, Quarona V, Zito A, Roato I, Morandi F, et al. NAD(þ)-Metabolizing ectoenzymes in remodeling tumor-host interactions: the human myeloma model. Cells 2015;4:520–37.
26. Waldschmidt JM, Simon A, Wider D, Muller SJ, Follo M, Ihorst G, et al. CXCL12 and CXCR7 are relevant targets to reverse cell adhesion-mediated drug resistance in multiple myeloma. Br J Haematol 2017;179:36–49.
27. McMillin DW, Delmore J, Weisberg E, Negri JM, Geer DC, Klippel S, et al. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med 2010;16:483–9.
28. van de Donk NWCJ, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood 2018;131:13–29.
29. Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, et al. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood 2016;128:959–70.
30. Nijhof IS, Groen RWJ, Lokhorst HM, van Kessel B, Bloem AC, van Velzen J, et al. Upregulation of CD38 expression on multiple myeloma cells by all-trans retinoic acid improves the efficacy of daratumumab. Leukemia 2015; 29:2039–49.
31. van der Veer MS, de Weers M, van Kessel B, Bakker JM, Wittebol S, Parren PWHI, et al. Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 2011; 96:284–90.
32. Beers SA, Chan CHT, James S, French RR, Attfield KE, Brennan CM, et al. Type II (tositumomab) anti-CD20 monoclonal antibody out performs type I (rituximab-like) reagents in B-cell depletion regardless of complement activation. Blood 2008;112:4170–7.
33. Shan D, Ledbetter JA, Press OW. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 1998;91:1644–52.
34. Deaglio S, Mehta K, Malavasi F. Human CD38: a (r)evolutionary story of enzymes and receptors. Leuk Res 2001;25:1–12.
35. Deaglio S, Aydin S, Vaisitti T, Bergui L, Malavasi F. CD38 at the junction between prognostic marker and therapeutic target. Trends Mol Med 2008; 14:210–8.
36. Deaglio S, Morra M, Mallone R, Ausiello CM, Prager E, Garbarino G, et al. Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member. J Immunol 1998;160:395–402.
37. Vijayan D, Young A, Teng MWL, Smyth MJ. Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer 2017;17:709–24.
38. Chen L, Diao L, Yang Y, Yi X, Rodriguez BL, Li Y, et al. CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discov 2018;8:1156–75.
39. Morandi F, Marimpietri D, Horenstein AL, Bolzoni M, Toscani D, Costa F, et al. Microvesicles released from multiple myeloma cells are equipped with ectoenzymes belonging to canonical and non-canonical adeno-sinergic pathways and produce adenosine from ATP and NAD. Oncoimmunology 2018;7:e1458809.
40. Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016;387:1551–60.
41. Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med 2015;373:1207–19.
42. Perez-Andres M, Paiva B, Nieto WG, Caraux A, Schmitz A, Almeida J, et al. Human peripheral blood B-cell compartments: a crossroad in B-cell traffic. Cytometry B Clin Cytom 2010;78:S47–60.
43. þ plasma cells. Haematologica 2010;95:1016–20.
44. Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, et al. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood 2016;127:3165–74.
45. Kohrt HE, Houot R, Goldstein MJ, Weiskopf K, Alizadeh AA, Brody J, et al. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood 2011;117:2423–32.