The Age of Immune-therapy in Multiple Myeloma with a Collective Goal for a Cure
Main Article Content
Abstract
Since the year 2000, we have seen unprecedented improvement in newly diagnosed multiple myeloma in terms of progression-free survival and a doubling of overall survival in 2009 from 2.5 years to 5 years. Patients treated now expect a median survival of 7.5 years, while those receiving quadruplet therapy, stem cell transplant, and consolidation and maintenance therapy have an expected survival up to 11 years.
Factors contributing to these improved outcomes include novel agents, antibodies, B-cell Maturation Agent-directed therapy, chimeric antigen receptor T-cells, bispecific antibodies, selective use of stem cell transplant, and supportive care measures such as bisphosphonates, prophylactic antimicrobials, cytokines, and intravenous immunoglobulins. Incorporation of these novel therapies in conjunction with increasing understanding of the genomic landscape of multiple myeloma and the evolving use of minimal residual disease negativity should persuade the oncology community to treat patients with high-risk smoldering multiple myeloma and guide treatment of early relapse in patients with newly diagnosed multiple myeloma. Here, we review early interventions within the context of genomic changes, minimal residual disease status, and strategies for treating high-risk smoldering multiple myeloma and standard and high-risk newly diagnosed multiple myeloma to improve progression-free survival, overall survival, and provide context for which patients may be considered cured.
Article Details
How to Cite
LARIOS, José M.; TEREBELO, Howard.
The Age of Immune-therapy in Multiple Myeloma with a Collective Goal for a Cure.
Medical Research Archives, [S.l.], v. 11, n. 10, oct. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/4607>. Date accessed: 23 nov. 2024.
doi: https://doi.org/10.18103/mra.v11i10.4607.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of Multiple Myeloma: ASCO and CCO Joint Clinical Practice Guideline [published correction appears in J Clin Oncol. 2020 Jul 20;38(21):2469]. J Clin Oncol. 2019;37(14):1228-1263. doi:10.1200/JCO.18.02096
2. SEER Cancer Statistics Review (CSR) 1975-2015. National Cancer Institute Surveillance, Epidemiology, and End Results. http://seer.cancer.gov/ Accessed November 2018
3. Terebelo H, Srinivasan S, Narang M, et al. Recognition of early mortality in multiple myeloma by a prediction matrix. Am J Hematol. 2017;92(9):915-923. doi:10.1002/ajh.24796
4. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582-2590. doi:10.1056/NEJMoa070389
5. Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438-447. doi:10.1056/NEJMoa1300439
6. Lonial S, Jacobus S, Fonseca R, et al. Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol. 2020;38(11):1126-1137. doi:10.1200/JCO.19.01740
7. Chojnacka M, Diamond B, Landgren O, Maura F. Defining genomic events involved in the evolutionary trajectories of myeloma and its precursor conditions. Semin Oncol. 2022; 49(1):11-18. doi:10.1053/j.seminoncol.2022.01.006
8. Bianchi G, Kyle RA, Larson DR, et al. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma. Leukemia. 2013;27(3):680-685. doi:10.1038/leu.2012.237
9. Misund K, Keane N, Stein CK, et al. MYC dysregulation in the progression of multiple myeloma. Leukemia. 2020;34(1):322-326. doi:10.1038/s41375-019-0543-4
10. Bustoros M, Sklavenitis-Pistofidis R, Park J, et al. Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression. J Clin Oncol. 2020;38(21):2380-2389. doi:10.1200/JCO.20.00437
11. Maura F, Petljak M, Lionetti M, et al. Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines. Leukemia. 2018;32(4):1044-1048. doi:10.1038/leu.2017.345.
12. Paiva B, Puig N, Cedena MT, et al. Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma. J Clin Oncol. 2020;38(8):784-792. doi:10.1200/JCO.19.01231
13. Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2022;40(25):2901-2912. doi:10.1200/JCO.21.01935
14. Murray DL, Puig N, Kristinsson S, et al. Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report. Blood Cancer J. 2021;11(2):24. Published 2021 Feb 1. doi:10.1038/s41408-021-00408-4
15. 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
16. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 trial. Lancet. 2016;387(10027):1551-1560. doi:10.1016/S0140-6736(15)01120-4
17. 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
18. 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
19. 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 randomized, multicenter, open-label, phase 3 study [published correction appears in Lancet. 2020 Aug 15;396(10249): 466]. Lancet. 2020;396(10245):186-197. doi:10.1016/S0140-6736(20)30734-0
20. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288
21. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomized, open-label, phase 3 study [published correction appears in Lancet. 2019 Jun 14;:]. Lancet. 2019;394(10192):29-38. doi:10.1016/S0140-6736(19)31240-1
22. Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
23. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicenter, open-label, randomized phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4
24. Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008;14(9):2775-2784. doi:10.1158/1078-0432.CCR-07-4246
25. Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373(7):621-631. doi:10.1056/NEJMoa1505654
26. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018;379(19):1811-1822. doi:10.1056/NEJMoa1805762
27. O'Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199(1):91-98. doi:10.1084/jem.20031330
28. Seckinger A, Delgado JA, Moser S, et al. Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment. Cancer Cell. 2017;31(3):396-410. doi:10.1016/j.ccell.2017.02.002
29. Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123(20):3128-3138. doi:10.1182/blood-2013-10-535088
30. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomized, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0
31. Duan D, Wang K, Wei C, et al. The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Front Immunol. 2021;12:609421. Published 2021 Mar 5. doi:10.3389/fimmu.2021.609421
32. Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019;380(18):1726-1737. doi:10.1056/NEJMoa1817226
33. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850
34. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CAR-TITUDE-1): a phase 1b/2 open-label study [published correction appears in Lancet. 2021 Oct 2;398(10307):1216]. Lancet. 2021;398(1029 7):314-324.
doi:10.1016/S0140-6736(21)00933-8
35. Mei H, Li C, Jiang H, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma. J Hematol Oncol. 2021;14(1):161. Published 2021 Oct 9. doi:10.1186/s13045-021-01170-7
36. Prommersberger S, Reiser M, Beckmann J, et al. CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma. Gene Ther. 2021;28(9):560-571. doi:10.1038/s41434-021-00254-w
37. Smith EL, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med. 2019;11(485): eaau7746. doi:10.1126/scitranslmed.aau7746
38. Mailankody S, Devlin SM, Landa J, et al. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022;387(13):1196-1206. doi:10.1056/NEJMoa2209900
39. Mailankody S, Matous JV, Chhabra S, et al. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results [published correction appears in Nat Med. 2023 Mar 17;:]. Nat Med. 2023;29(2):422-429. doi:10.1038/s41591-022-02182-7
40. Dahlén E, Veitonmäki N, Norlén P. Bispecific antibodies in cancer immunotherapy. Ther Adv Vaccines Immunother. 2018;6(1):3-17.
41. Cho SF, Yeh TJ, Anderson KC, Tai YT. Bispecific antibodies in multiple myeloma treatment: A journey in progress. Front Oncol. 2022;12: 1032775. Published 2022 Oct 18. doi:10.3389/fonc.2022.1032775
42. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478
43. Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 monumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb) for relapsed/refractory multiple myeloma (RRMM). ASCO Meeting 2022. Abstract 8036.
44. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results [published online ahead of print, 2023 Aug 15]. Nat Med. 2023;10.1038/s41591-023-02528-9. doi:10.1038/s41591-023-02528-9
45. Li J, Stagg NJ, Johnston J, et al. Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing. Cancer Cell. 2017;31(3):383-395. doi:10.1016/j.ccell.2017.02.001
46. Cohen AD, Harrison MJ, Krishnan A, et al. Initial clinical activity and safety of BFCR4350A, a FcRH5/CD3 T-cell engaging bispecific antibody, in relapsed/refractory multiple myeloma. Blood (2020) 136 (supplement 1): 42-43.
47. Pouleau B, Estoppey C, Suere P, et al. Preclinical characterization of ISB 1342, a CD38 × CD3 T-cell engager for relapsed/refractory multiple myeloma. Blood. 2023;142(3):260-273. doi:10.1182/blood.2022019451
48. Jagannath S, Heffner LT Jr, Ailawadhi S, et al. Indatuximab Ravtansine (BT062) Monotherapy in Patients With Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019;19(6):372-380. doi:10.1016/j.clml.2019.02.006
49. Kelly KR, Ailawadhi S, Siegel DS, et al. Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicenter, phase 1/2a study. Lancet Haematol. 2021;8(11):e794-e807. doi:10.1016/S2352-3026(21)00208-8
50. Gantke T, Reusch U, Kellner C, et al. AFM26 is a novel, highly potent BCMA/CD16a-directed bispecific antibody for high affinity NK-cell engagement in multiple myeloma. ASCO Meeting 2017. Abstract 8045.
51. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750
52. Perrot A, Lauwers-Cances V, Cazaubiel T, et al. Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow up Analysis of the IFM 2009 Trial. Blood 2020; 36 (Supplement 1): 39,
53. McCAR-Thy PL, Holstein SA, Petrucci MT, et al. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017;35(29):3279-3289. doi:10.1200/JCO.2017.72.6679
54. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomized, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6.
55. Lonial S, Popat R, Hulin C, et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicenter, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022;9(11):e822-e832. doi:10.1016/S2352-3026(22)00290-3.
56. Richardson PG, Trudel S, Popat R, et al. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023;389(11):1009-1022. doi:10.1056/NEJMoa2303194
57. Rodriguez-Otero P, Paiva B, San-Miguel JF. Roadmap to cure multiple myeloma. Cancer Treat Rev. 2021;100:102284. doi:10.1016/j.ctrv.2021.102284.
2. SEER Cancer Statistics Review (CSR) 1975-2015. National Cancer Institute Surveillance, Epidemiology, and End Results. http://seer.cancer.gov/ Accessed November 2018
3. Terebelo H, Srinivasan S, Narang M, et al. Recognition of early mortality in multiple myeloma by a prediction matrix. Am J Hematol. 2017;92(9):915-923. doi:10.1002/ajh.24796
4. Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582-2590. doi:10.1056/NEJMoa070389
5. Mateos MV, Hernández MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438-447. doi:10.1056/NEJMoa1300439
6. Lonial S, Jacobus S, Fonseca R, et al. Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol. 2020;38(11):1126-1137. doi:10.1200/JCO.19.01740
7. Chojnacka M, Diamond B, Landgren O, Maura F. Defining genomic events involved in the evolutionary trajectories of myeloma and its precursor conditions. Semin Oncol. 2022; 49(1):11-18. doi:10.1053/j.seminoncol.2022.01.006
8. Bianchi G, Kyle RA, Larson DR, et al. High levels of peripheral blood circulating plasma cells as a specific risk factor for progression of smoldering multiple myeloma. Leukemia. 2013;27(3):680-685. doi:10.1038/leu.2012.237
9. Misund K, Keane N, Stein CK, et al. MYC dysregulation in the progression of multiple myeloma. Leukemia. 2020;34(1):322-326. doi:10.1038/s41375-019-0543-4
10. Bustoros M, Sklavenitis-Pistofidis R, Park J, et al. Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression. J Clin Oncol. 2020;38(21):2380-2389. doi:10.1200/JCO.20.00437
11. Maura F, Petljak M, Lionetti M, et al. Biological and prognostic impact of APOBEC-induced mutations in the spectrum of plasma cell dyscrasias and multiple myeloma cell lines. Leukemia. 2018;32(4):1044-1048. doi:10.1038/leu.2017.345.
12. Paiva B, Puig N, Cedena MT, et al. Measurable Residual Disease by Next-Generation Flow Cytometry in Multiple Myeloma. J Clin Oncol. 2020;38(8):784-792. doi:10.1200/JCO.19.01231
13. Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2022;40(25):2901-2912. doi:10.1200/JCO.21.01935
14. Murray DL, Puig N, Kristinsson S, et al. Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report. Blood Cancer J. 2021;11(2):24. Published 2021 Feb 1. doi:10.1038/s41408-021-00408-4
15. 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
16. Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 trial. Lancet. 2016;387(10027):1551-1560. doi:10.1016/S0140-6736(15)01120-4
17. 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
18. 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
19. 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 randomized, multicenter, open-label, phase 3 study [published correction appears in Lancet. 2020 Aug 15;396(10249): 466]. Lancet. 2020;396(10245):186-197. doi:10.1016/S0140-6736(20)30734-0
20. Voorhees PM, Kaufman JL, Laubach J, et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020;136(8):936-945. doi:10.1182/blood.2020005288
21. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomized, open-label, phase 3 study [published correction appears in Lancet. 2019 Jun 14;:]. Lancet. 2019;394(10192):29-38. doi:10.1016/S0140-6736(19)31240-1
22. Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med. 2019;380(22):2104-2115. doi:10.1056/NEJMoa1817249
23. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicenter, open-label, randomized phase 3 trial. Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4
24. Hsi ED, Steinle R, Balasa B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res. 2008;14(9):2775-2784. doi:10.1158/1078-0432.CCR-07-4246
25. Lonial S, Dimopoulos M, Palumbo A, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015;373(7):621-631. doi:10.1056/NEJMoa1505654
26. Dimopoulos MA, Dytfeld D, Grosicki S, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018;379(19):1811-1822. doi:10.1056/NEJMoa1805762
27. O'Connor BP, Raman VS, Erickson LD, et al. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199(1):91-98. doi:10.1084/jem.20031330
28. Seckinger A, Delgado JA, Moser S, et al. Target Expression, Generation, Preclinical Activity, and Pharmacokinetics of the BCMA-T Cell Bispecific Antibody EM801 for Multiple Myeloma Treatment. Cancer Cell. 2017;31(3):396-410. doi:10.1016/j.ccell.2017.02.002
29. Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123(20):3128-3138. doi:10.1182/blood-2013-10-535088
30. Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomized, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207-221. doi:10.1016/S1470-2045(19)30788-0
31. Duan D, Wang K, Wei C, et al. The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Front Immunol. 2021;12:609421. Published 2021 Mar 5. doi:10.3389/fimmu.2021.609421
32. Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2019;380(18):1726-1737. doi:10.1056/NEJMoa1817226
33. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021;384(8):705-716. doi:10.1056/NEJMoa2024850
34. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CAR-TITUDE-1): a phase 1b/2 open-label study [published correction appears in Lancet. 2021 Oct 2;398(10307):1216]. Lancet. 2021;398(1029 7):314-324.
doi:10.1016/S0140-6736(21)00933-8
35. Mei H, Li C, Jiang H, et al. A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma. J Hematol Oncol. 2021;14(1):161. Published 2021 Oct 9. doi:10.1186/s13045-021-01170-7
36. Prommersberger S, Reiser M, Beckmann J, et al. CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free Sleeping Beauty gene transfer to treat multiple myeloma. Gene Ther. 2021;28(9):560-571. doi:10.1038/s41434-021-00254-w
37. Smith EL, Harrington K, Staehr M, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med. 2019;11(485): eaau7746. doi:10.1126/scitranslmed.aau7746
38. Mailankody S, Devlin SM, Landa J, et al. GPRC5D-Targeted CAR T Cells for Myeloma. N Engl J Med. 2022;387(13):1196-1206. doi:10.1056/NEJMoa2209900
39. Mailankody S, Matous JV, Chhabra S, et al. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results [published correction appears in Nat Med. 2023 Mar 17;:]. Nat Med. 2023;29(2):422-429. doi:10.1038/s41591-022-02182-7
40. Dahlén E, Veitonmäki N, Norlén P. Bispecific antibodies in cancer immunotherapy. Ther Adv Vaccines Immunother. 2018;6(1):3-17.
41. Cho SF, Yeh TJ, Anderson KC, Tai YT. Bispecific antibodies in multiple myeloma treatment: A journey in progress. Front Oncol. 2022;12: 1032775. Published 2022 Oct 18. doi:10.3389/fonc.2022.1032775
42. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478
43. Schinke CD, Touzeau C, Minnema MC, et al. Pivotal phase 2 monumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb) for relapsed/refractory multiple myeloma (RRMM). ASCO Meeting 2022. Abstract 8036.
44. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results [published online ahead of print, 2023 Aug 15]. Nat Med. 2023;10.1038/s41591-023-02528-9. doi:10.1038/s41591-023-02528-9
45. Li J, Stagg NJ, Johnston J, et al. Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing. Cancer Cell. 2017;31(3):383-395. doi:10.1016/j.ccell.2017.02.001
46. Cohen AD, Harrison MJ, Krishnan A, et al. Initial clinical activity and safety of BFCR4350A, a FcRH5/CD3 T-cell engaging bispecific antibody, in relapsed/refractory multiple myeloma. Blood (2020) 136 (supplement 1): 42-43.
47. Pouleau B, Estoppey C, Suere P, et al. Preclinical characterization of ISB 1342, a CD38 × CD3 T-cell engager for relapsed/refractory multiple myeloma. Blood. 2023;142(3):260-273. doi:10.1182/blood.2022019451
48. Jagannath S, Heffner LT Jr, Ailawadhi S, et al. Indatuximab Ravtansine (BT062) Monotherapy in Patients With Relapsed and/or Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2019;19(6):372-380. doi:10.1016/j.clml.2019.02.006
49. Kelly KR, Ailawadhi S, Siegel DS, et al. Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicenter, phase 1/2a study. Lancet Haematol. 2021;8(11):e794-e807. doi:10.1016/S2352-3026(21)00208-8
50. Gantke T, Reusch U, Kellner C, et al. AFM26 is a novel, highly potent BCMA/CD16a-directed bispecific antibody for high affinity NK-cell engagement in multiple myeloma. ASCO Meeting 2017. Abstract 8045.
51. Attal M, Lauwers-Cances V, Hulin C, et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017;376(14):1311-1320. doi:10.1056/NEJMoa1611750
52. Perrot A, Lauwers-Cances V, Cazaubiel T, et al. Early Versus Late Autologous Stem Cell Transplant in Newly Diagnosed Multiple Myeloma: Long-Term Follow up Analysis of the IFM 2009 Trial. Blood 2020; 36 (Supplement 1): 39,
53. McCAR-Thy PL, Holstein SA, Petrucci MT, et al. Lenalidomide Maintenance After Autologous Stem-Cell Transplantation in Newly Diagnosed Multiple Myeloma: A Meta-Analysis. J Clin Oncol. 2017;35(29):3279-3289. doi:10.1200/JCO.2017.72.6679
54. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomized, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6.
55. Lonial S, Popat R, Hulin C, et al. Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicenter, multicohort, open-label, phase 1/2 trial. Lancet Haematol. 2022;9(11):e822-e832. doi:10.1016/S2352-3026(22)00290-3.
56. Richardson PG, Trudel S, Popat R, et al. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023;389(11):1009-1022. doi:10.1056/NEJMoa2303194
57. Rodriguez-Otero P, Paiva B, San-Miguel JF. Roadmap to cure multiple myeloma. Cancer Treat Rev. 2021;100:102284. doi:10.1016/j.ctrv.2021.102284.