Daratumumab – Hope for Myeloma Patients, a Challenge for Clinical Laboratories
Authors:
T. Jelínek 1,2; M. Kořístka 3; Z. Čermáková 3; R. Hájek 1
Authors‘ workplace:
Klinika hematoonkologie LF OU a FN Ostrava
1; Přírodovědecká fakulta OU v Ostravě
2; Krevní centrum, FN Ostrava
3
Published in:
Klin Onkol 2017; 30(1): 13-19
Category:
Review
doi:
https://doi.org/10.14735/amko201713
Overview
Monoclonal antibodies represent a standard part in the treatment of oncologic patients, but their efficacy in multiple myeloma used to be unsatisfactory. Daratumumab monotherapy was approved by the American FDA in 2015, after unprecedented results were obtained in a heavily pre-treated group of patients. In 2016 daratumumab was approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of myeloma patients who have received at least one prior therapy.The toxicity of the drug is low, and is dominated by infusion-related reactions in more or less half of patients. The development as well as the management of these sometimes urgent reactions is described in depth in this review. As multiple myeloma is characterized by the presence of paraprotein (monoclonal antibody) and CD38 is a ubiquitous antigen, several unexpected complications have been reported during the administration of the drug. In this review, we aim to describe and offer some solutions for the complications that may be encountered during daratumumab treatment, such as interference with serum protein electrophoresis and immunofixation assays that may confuse the assessment of the hematological response, interference with blood compatibility testing that may cause a delay in the delivery of compatible transfusions, and difficulties that may occur in flow cytometric analysis of minimal residual disease. Because of the high activity of daratumumab and its expected widespread use, clinicians should be aware of its side effects and their management. It is also very important to inform colleagues in clinical laboratories about the initiation of daratumumab treatment in particular patient.
Key words:
multiple myeloma – daratumumab – infusion related reaction – flow cytometry – transfusion
This work was supported by the Czech Ministry of Education, Youth and Sports (project no. IRP- 201550) and by the Czech Ministry of Health (15-29667A).
The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Accepted:
22. 8. 2016
Submitted:
12. 5. 2016
Sources
1. Sant M, Allemani C, Tereanu C et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116 (19): 3724–3734. doi: 10.1182/blood-2010-05-282632.
2. Hájek R, Krejcí M, Pour L et al. Multiple myeloma. Klin Onkol 2011; 24 (Suppl): S10–S13.
3. San-Miguel JF, Mateos MV. Can multiple myeloma become a curable disease? Haematologica 2011; 96 (9): 1246–1248. doi: 10.3324/haematol.2011.051169.
4. Barlogie B, Mitchell A, van Rhee F et al. Curing myeloma at last: defining criteria and providing the evidence. Blood 2014; 124 (20): 3043–3051. doi: 10.1182/blood-2014-07-552059.
5. Sedlarikova L, Kubiczkova L, Sevcikova S et al. Mechanism of immunomodulatory drugs in multiple myeloma. Leuk Res 2012; 36 (10): 1218–1224. doi: 10.1016/j.leukres.2012.05.010.
6. Kubiczková L, Matějíková J, Sedlaříková L et al. Proteasome inhibitors in treatment of multiple myeloma. Klin Onkol 2013; 26 (1): 11–18. doi: 10.14735/amko201311.
7. Jelinek T, Hajek R. Monoclonal antibodies – a new era in the treatment of multiple myeloma. Blood Rev 2016; 30 (2): 101–110. doi: 10.1016/j.blre.2015.08.004.
8. Hannon JL, Clarke G. Transfusion management of patients receiving daratumumab therapy for advanced plasma cell myeloma. Transfusion 2015; 55 (11): 2770. doi: 10.1111/trf.13267.
9. 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. doi: 10.1182/blood-2015-10-646810.
10. Malavasi F, Funaro A, Roggero S et al. Human CD38: a glycoprotein in search of a function. Immunol Today 1994; 15 (3): 95–97.
11. 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. doi: 10.1152/physrev.00035.2007.
12. Deaglio S, Mehta K, Malavasi F. Human CD38: a (r) evolutionary story of enzymes and receptors. Leuk Res 2001; 25 (1): 1–12.
13. Lin P, Owens R, Tricot G et al. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 2004; 121 (4): 482–488.
14. Damle RN, Wasil T, Fais F et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94 (6): 1840–1847.
15. Marinov J, Koubek K, Starý J. Immunophenotypic significance of the “lymphoid” CD38 antigen in myeloid blood malignancies. Neoplasma 1993; 40 (6): 355–358.
16. Deaglio S, Zubiaur M, Gregorini A et al. Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells. Blood 2002; 99 (7): 2490–2498.
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. doi: 10.1080/19420862.2015.1007813.
18. 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 Baltim Md 1950; 186 (3): 1840–1848.
19. van de Donk NW, Janmaat ML, Mutis T et al. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev 2016; 270 (1): 95–112.
20. Nijhof IS, Groen RW, Noort WA 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 (12): 2802–2810. doi: 10.1158/1078-0432.CCR-14-1813.
21. Nijhof IS, Lammerts van Bueren JJ, van Kessel B 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 (2): 263–268. doi: 10.3324/haematol.2014.117531.
22. Jelinek T, Hajek R. Monoclonal antibodies – a new era in the treatment of multiple myeloma. Blood Rev [online]. [cited 2015 Dec 9]. Available from: www.bloodreviews.com/article/S0268960X1500065X/abstract.
23. 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. doi: 10.1182/blood-2011-06-360552.
24. 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. doi: 10.1056/NEJMoa1506348.
25. 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. doi: 10.1016/S0140-6736 (15) 01120-4.
26. Plesner T, Arkenau HT, Gimsing P et al. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood 2016; 128: 1821–1828. doi: 10.1182/blood-2016-07-726729.
27. 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. Blood 2015; 126 (23): 508.
28. Palumbo A, Chanan-Khan A, Weisel K et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375 (8): 754–766. doi: 10.1056/NEJMoa1606038.
29. Dimopoulos MA, Oriol A, Nahi H et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375 (14): 1319–1331. doi: 10.1056/NEJMoa1607751.
30. Durie BG, Harousseau JL, Miguel JS et al. International uniform response criteria for multiple myeloma. Leukemia 2006; 20 (9): 1467–1473.
31. McCudden CR, Voorhees PM, Hainsworth SA et al. Interference of monoclonal antibody therapies with serum protein electrophoresis tests. Clin Chem 2010; 56 (12): 1897–1899. doi: 10.1373/clinchem.2010.152116.
32. Ruinemans-Koerts J, Verkroost C, Schmidt-Hieltjes Y et al. Interference of therapeutic monoclonal immunoglobulins in the investigation of M-proteins. Clin Chem Lab Med 2014; 52 (11): e235–e237. doi: 10.1515/cclm-2013-0898.
33. van de Donk NW, Otten HG, El Haddad O et al. Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA). Clin Chem Lab Med 2016; 54 (6): 1005–1109. doi: 10.1515/cclm-2015-0888.
34. Paiva B, van Dongen JJ, Orfao A. New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood 2015; 125 (20): 3059–3068. doi: 10.1182/blood-2014-11-568907.
35. Paiva B, Vidriales MB, Cerveró J et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 2008; 112 (10): 4017–4023. doi: 10.1182/blood-2008-05-159 624.
36. Arroz M, Came N, Lin P et al. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry B Clin Cytom 2016; 90 (1): 31–39. doi: 10.1002/cyto.b.21228.
37. Paiva B, Puig N, García-Sanz R et al. Is this the time to introduce minimal residual disease in multiple myeloma clinical practice? Clin Cancer Res 2015; 21 (9): 2001–2008. doi: 10.1158/1078-0432.CCR-14-2841.
38. Rawstron AC, Orfao A, Beksac M et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008; 93 (3): 431–438. doi: 10.3324/haematol.11080.
39. Pojero F, Flores-Montero J, Sanoja L et al. Utility of CD54, CD229, and CD319 for the identification of plasma cells in patients with clonal plasma cell diseases. Cytometry B Clin Cytom 2016; 90 (1): 91–100. doi: 10.1002/cyto.b.21269.
40. Anti-human CD38 multi-epitope reagent [Internet]. [cited 2016 Mar 19]. Available from: www.cytognos.com/index.php/en/reagents/antibodies/1446-anti-human-cd38-multiepitope-reagent.
41. Oostendorp M, Lammerts van Bueren JJ, Doshi P et al. When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy. Transfusion 2015; 55 (6 Pt 2): 1555–1562. doi: 10.1111/trf.13150.
42. Chapuy CI, Nicholson RT, Aguad MD et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015; 55 (6 Pt 2): 1545–1554. doi: 10.1111/trf.13069.
43. De Vooght KM, Oostendorp M, van Solinge WW. Dealing with anti-CD38 (daratumumab) interference in blood compatibility testing. Transfusion 2016; 56 (3): 778–779. doi: 10.1111/trf.13474.
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Clinical Oncology
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