Antibody-Based Treatment Approaches in Multiple Myeloma

Overview

Journal Curr Hematol Malig Rep

Publisher Current Science

Specialties Hematology
Oncology

Date 2021 Mar 17

PMID 33730360

Citations 8

Authors

Hitomi Hosoya

Surbhi Sidana

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: The field of multiple myeloma treatment has entered a new era with antibody-based approaches in clinical practice. In this review, we focus on the clinical approaches of utilizing antibody-based modality, specifically monoclonal antibodies, antibody-drug conjugates, and bispecific T-cell antibodies in the treatment of multiple myeloma.

Recent Findings: Three monoclonal antibodies (daratumumab, isatuximab, elotuzumab) and one anti-BCMA (B-cell maturation antigen) antibody-drug conjugate (belantamab mafodotin) have been approved by the FDA in the last 5 years for the treatment of multiple myeloma. There are many ongoing clinical trials using novel targets and constructs, including bispecific antibodies against BCMA, GPRC5D, and FCRH5. In addition to exploring efficacy, there are ongoing efforts to overcome the resistance to therapy. Antibody-based therapy has improved the outcomes of patients with multiple myeloma and has been incorporated in the standard of care. We expect to see novel targets and constructs that can achieve a deeper and more durable response while minimizing toxicity, as well as better strategies for toxicity management for existing agents. We also expect that antibody-based strategies will be used in earlier lines of therapy in the future.

Citing Articles

Lymphocyte profile in peripheral blood of patients with multiple myeloma.

Dekojova T, Gmucova H, Maceckova D, Klieber R, Ostasov P, Leba M Ann Hematol. 2024; 103(12):5615-5625.

PMID: 38832999 DOI: 10.1007/s00277-024-05820-x.

Efficacy of elotuzumab for multiple myeloma deteriorates after daratumumab: a multicenter retrospective study.

Nakamura N, Arima N, Takakuwa T, Yoshioka S, Imada K, Fukushima K Ann Hematol. 2024; 103(12):5681-5690.

PMID: 38492020 DOI: 10.1007/s00277-024-05705-z.

Monoclonal Antibodies: The Greatest Resource to Treat Multiple Myeloma.

Luca F, Allegra A, Di Chio C, Previti S, Zappala M, Ettari R Int J Mol Sci. 2023; 24(4).

PMID: 36834545 PMC: 9959320. DOI: 10.3390/ijms24043136.

Idecabtagene Vicleucel for Relapsed/Refractory Multiple Myeloma: Real-World Experience From the Myeloma CAR T Consortium.

Hansen D, Sidana S, Peres L, Colin Leitzinger C, Shune L, Shrewsbury A J Clin Oncol. 2023; 41(11):2087-2097.

PMID: 36623248 PMC: 10082273. DOI: 10.1200/JCO.22.01365.

Kinase Inhibition in Multiple Myeloma: Current Scenario and Clinical Perspectives.

Barreto I, Machado C, Almeida D, DE Pinho Pessoa F, Gadelha R, da Costa Pantoja L Pharmaceutics. 2022; 14(9).

PMID: 36145532 PMC: 9506264. DOI: 10.3390/pharmaceutics14091784.

References

Jakubowiak A, Offidani M, Pegourie B, Rubia J, Garderet L, Laribi K . Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016; 127(23):2833-40. PMC: 4900953. DOI: 10.1182/blood-2016-01-694604. View

Madry C, Laabi Y, Callebaut I, Roussel J, Hatzoglou A, Le Coniat M . The characterization of murine BCMA gene defines it as a new member of the tumor necrosis factor receptor superfamily. Int Immunol. 1998; 10(11):1693-702. DOI: 10.1093/intimm/10.11.1693. View

Birrer M, Moore K, Betella I, Bates R . Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst. 2019; 111(6):538-549. DOI: 10.1093/jnci/djz035. View

Kitadate A, Kobayashi H, Abe Y, Narita K, Miura D, Takeuchi M . Pre-treatment CD38-positive regulatory T cells affect the durable response to daratumumab in relapsed/refractory multiple myeloma patients. Haematologica. 2019; 105(1):e37-e40. PMC: 6939519. DOI: 10.3324/haematol.2019.219683. View

Lonial S, Weiss B, Usmani S, Singhal S, Chari A, Bahlis N . 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. View

Topp M, Duell J, Zugmaier G, Attal M, Moreau P, Langer C . Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020; 38(8):775-783. DOI: 10.1200/JCO.19.02657. View

Voorhees P, Kaufman J, Laubach J, Sborov D, Reeves B, Rodriguez C . Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136(8):936-945. PMC: 7441167. DOI: 10.1182/blood.2020005288. View

Moreno L, Perez C, Zabaleta A, Manrique I, Alignani D, Ajona D . The Mechanism of Action of the Anti-CD38 Monoclonal Antibody Isatuximab in Multiple Myeloma. Clin Cancer Res. 2019; 25(10):3176-3187. DOI: 10.1158/1078-0432.CCR-18-1597. View

Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I . Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015; 373(7):621-31. DOI: 10.1056/NEJMoa1505654. View

10.

Claudio J, Masih-Khan E, Tang H, Goncalves J, Voralia M, Li Z . A molecular compendium of genes expressed in multiple myeloma. Blood. 2002; 100(6):2175-86. DOI: 10.1182/blood-2002-01-0008. View

11.

Saltarella I, Desantis V, Melaccio A, Solimando A, Lamanuzzi A, Ria R . Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma. Cells. 2020; 9(1). PMC: 7017193. DOI: 10.3390/cells9010167. View

12.

Baeuerle P, Reinhardt C . Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009; 69(12):4941-4. DOI: 10.1158/0008-5472.CAN-09-0547. View

13.

Mateos M, Dimopoulos M, Cavo M, Suzuki K, Jakubowiak A, Knop S . Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2017; 378(6):518-528. DOI: 10.1056/NEJMoa1714678. View

14.

Veillette A, Guo H . CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma. Crit Rev Oncol Hematol. 2013; 88(1):168-77. DOI: 10.1016/j.critrevonc.2013.04.003. View

15.

Mills J, Kohlhagen M, Willrich M, Kourelis T, Dispenzieri A, Murray D . A universal solution for eliminating false positives in myeloma due to therapeutic monoclonal antibody interference. Blood. 2018; 132(6):670-672. DOI: 10.1182/blood-2018-05-848986. View

16.

Tai Y, Anderson K . Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015; 7(11):1187-99. PMC: 4976846. DOI: 10.2217/imt.15.77. View

17.

Huehls A, Coupet T, Sentman C . Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 2014; 93(3):290-6. PMC: 4445461. DOI: 10.1038/icb.2014.93. View

18.

van de Donk N, Janmaat M, Mutis T, Lammerts van Bueren J, Ahmadi T, Sasser A . Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev. 2016; 270(1):95-112. PMC: 4755228. DOI: 10.1111/imr.12389. View

19.

Zonder J, Mohrbacher A, Singhal S, van Rhee F, Bensinger W, Ding H . A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood. 2011; 120(3):552-9. PMC: 4467882. DOI: 10.1182/blood-2011-06-360552. View

20.

Flores-Montero J, Sanoja-Flores L, Paiva B, Puig N, Garcia-Sanchez O, Bottcher S . Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017; 31(10):2094-2103. PMC: 5629369. DOI: 10.1038/leu.2017.29. View