Isatuximab, a novel anti-CD38 monoclonal antibody in the treatment of multiple myeloma: efficacy and safety

Cover Page

Cite item

Full Text

Abstract

The article discusses the place of CD38 antibodies in the treatment of multiple myeloma (MM). Special emphasis is put of isatuximab. In 2020, isatuximab in combination with pomalidomide and dexamethasone was approved in Russia for the treatment of adult patients with MM who have received at least two lines therapies, including lenalidomide and a proteasome inhibitor. The published data from studies of isatuximab, demonstrating its clinical efficacy and safety in combination with standard treatment regimens for recurrent/refractory MM, are discussed.

About the authors

Karina E. Zatolochina

Peoples’ Friendship University of Russia (RUDN University)

Author for correspondence.
Email: kapelovich@hpmp.ru
ORCID iD: 0000-0003-0925-0623

Cand. Sci. (Med.)

Russian Federation, Moscow

Sergey K. Zyryanov

Peoples’ riendship University of Russia (RUDN University); City Clinical Hospital №24

Email: kapelovich@hpmp.ru
ORCID iD: 0000-0002-6348-6867

D. Sci. (Med.), Prof.

Russian Federation, Moscow; Moscow

Elena A. Ushkalova

Peoples’ Friendship University of Russia (RUDN University)

Email: kapelovich@hpmp.ru
ORCID iD: 0000-0003-4165-1726

D. Sci. (Med.), Prof.

Russian Federation, Moscow

References

  1. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019 [Malignant tumors of Russia in 2018 (morbidity and mortality). Ed. AD Kaprin ,VV Starinskii, GV Petrova. Moscow: P. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre, 2019 (in Russian)].
  2. Van de Donk N, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood. 2018;131:13-29. doi: 10.1182/blood-2017-06-740944
  3. McKeage K. Daratumumab: First Global Approval. Drugs. 2016;76(2):275-81. doi: 10.1007/s40265-015-0536-1
  4. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207-19. doi: 10.1056/NEJMoa1506348
  5. 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;387:1551-60. doi: 10.1016/S0140-6736(15)01120-4
  6. Usmani SZ, Weiss BM, Plesner T, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128:37-44. doi: 10.1182/blood-2016-03-705210
  7. Palumbo A, Chanan-Khan A, Weisel K, et al. CASTOR Investigators. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754-66. doi: 10.1056/NEJMoa1606038
  8. Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Haematologica. 2018;103:2079-87. doi: 10.3324/haematol.2018.194118
  9. Dimopoulos MA, Oriol A, Nahi H, et al. POLLUX Investigators. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319-31. doi: 10.1056/NEJMoa1607751
  10. Dimopoulos MA, San-Miguel J, Belch A, et al. Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Haematologica. 2018;103:2088-96. doi: 10.3324/haematol.2018.194282
  11. Bahlis NJ, Dimopoulos MA, White DJ, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia. 2020;34:1875-84. doi: 10.1038/s41375-020-0711-6
  12. Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, openlabel, phase 3 study. Lancet. 2020;396:186-97. doi: 10.1016/S0140-6736(20)30734-0
  13. Dhillon S. Isatuximab: First Approval. Drugs. 2020;80:905-12. doi: 10.1007/s40265-020-01311-1
  14. Attal M, Richardson PG, Rajkumar SV, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019;394(10214):2096-107. doi: 10.1016/S0140-6736(19)32556-5
  15. Richardson PG, Attal M, Campana F, et al. Isatuximab plus pomalidomide/dexamethasone versus pomalidomide/dexamethasone in relapsed/refractory multiple myeloma: ICARIA Phase III study design. Future Oncol. 2018;14(11):1035-47. doi: 10.2217/fon-2017-0616
  16. Dimopoulos MA, Leleu X, Moreau P, et al. Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis. Leukemia. 2021;35:562-72. doi: 10.1038/s41375-020-0868-z
  17. Harrison SJ, Richardson PG, Alegre A, et al. Efficacy of isatuximab/pomalidomide/dexamethasone in relapsed/refractory multiple myeloma: ICARIA-MM high-risk cytogenetics subgroup analysis. Clin Lymphoma Myeloma Leukemia. 2019;19(10 Suppl.):e33. doi: 10.1016/j.clml.2019.09.049
  18. Beksac M, Richardson PG, Unal A, et al. Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma and soft-tissue plasmacytomas: ICARIA-MM subgroup analysis. EHA. 2020;abstract #EP978. Available at: https://library.ehaweb.org/eha/2020/eha25th/294895/meral.beksac.isatuximab.plus.pomalidomide.and.dexamethasone.in.patients.with.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dicaria. Accessed: 30.03.2021.
  19. Dimopoulos M, Campana F, Bury DP, et al. Health-related quality of life in heavily pre-treated and renally impaired patients with relapsed/refractory multiple myeloma receiving isatuximab plus pomalidomide and dexamethasone: ICARIA-MM study. EHA. 2020;abstract #EP1028. Available at: https://library.ehaweb.org/eha/2020/eha25th/293518/meletios.dimopoulos.health-related.quality.of.life.in.heavily.pre-treated.and.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Asearch%3Dquality+of+life. Accessed: 30.03.2021.
  20. Schjesvold FH, Richardson PG, Attal M, et al. Efficacy of isatuximab with pomalidomide and dexamethasone in elderly patients with relapsed/refractory multiple myeloma: ICARIAMM subgroup analysis. Blood. 2019;134(Suppl.):1893. doi: 10.1182/blood-2019-128010
  21. Dimopoulos MA, Leleu X, Moreau P, et al. Effect of isatuximab plus pomalidomide/dexamethasone on renal impairment in relapsed/refractory multiple myeloma: ICARIA-MM study subgroup analysis. Clin Lymphoma Myeloma Leukemia. 2019;19(10 Suppl.):e254. doi: 10.1016/j.clml.2019.09.420
  22. Ikeda T, Sunami K, Huang SY, et al. Efficacy and safety of isatuximab plus pomalidomide and dexamethasone in East Asian patients with relapsed/refractory multiple myeloma: a subgroup analysis of ICARIA-MM study. Ann Oncol. 2019;30(Suppl. 9):ix92. doi: 10.1093/annonc/mdz427.003
  23. Moreau P, Dimopoulos MA, Yong K, et al. Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design. Future Oncol. 2020;16(2):4347-58. doi: 10.2217/fon-2019-0431
  24. Moreau P, Dimopoulos MA, Yong K, et al. Isatuximab Plus Carfilzomib and Dexamethasone Vs Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma (IKEMA): Interim Analysis of a Phase 3, Randomized, Open-Label Study. 62nd ASH Annual Meeting and Exposition. 2020. Available at: https://ash.confex.com/ash/2020/webprogram/Paper134573.html. Accessed: 30.03.2021.
  25. Orlowski RZ, Goldschmidt H, Cavo M, et al. Phase III (IMROZ) study design: Isatuximab plus bortezomib (V), lenalidomide (R), and dexamethasone (D) vs VRd in transplant-ineligible patients (PTS) with newly diagnosed multiple myeloma (NDMM). JCO. 2018;36:TPS8055. doi: 10.1200/JCO.2018.36.15_suppl.TPS8055
  26. Martin T, Baz R, Benson DM, et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017;129(25):3294-303. doi: 10.1182/blood-2016-09-740787
  27. Asemissen AM, Autenrieth S, Bieber K, et al. Prospective monitoring of immune signatures in newly diagnosed high risk multiple myeloma patients under treatment with isatuximab, carfilzomib, lenalidomide and dexamethasone (I-KRd): first results of the GMMG-CONCEPT trial. Clin Lymphoma Myeloma Leukemia. 2019;19(10 Suppl.):e141–2. doi: 10.1016/j.clml.2019.09.236
  28. Ocio EM, Bringhen S, Oliva S, et al. A phase Ib study of isatuximab in combination with bortezomib, cyclophosphamide, and dexamethasone (VCDI) in patients with newly diagnosed multiple myeloma non-eligible for transplantation. Blood. 2017;130(Suppl.):3160. doi: 10.1182/blood.V130.Suppl_1.3160.3160
  29. Kumar SK, Callander NS, Adekola K, et al. Multiple Myeloma, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(12):1685-717. doi: 10.6004/jnccn.2020.0057

Copyright (c) 2021 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies