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Targeting BCMA in Multiple Myeloma: Evidence-Based Guidance for Current and Near Future Clinical Integration
  • CME

Nina Shah, MD
Released: April 4, 2022
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References

  1. Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2018;9:1821.
  2. Yu B, Jiang T, Liu D. BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol. 2020;13:125.
  3. 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;123:3128-3138.
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  5. Lonial S, Lee HC, Badros A, et al. Longer term outcomes with single-agent belantamab mafodotin in patients with relapsed or refractory multiple myeloma: 13-month follow-up from the pivotal DREAMM-2 study. Cancer. 2021;127:4198-4212.
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  8. Popat R, Nooka A, Stockerl-Goldstein K, et al. DREAMM-6: safety, tolerability and clinical activity of belantamab mafodotin (belamaf) in combination with bortezomib/dexamethasone (bordex) in relapsed/refractory multiple myeloma (RRMM). Presented at: 62nd Annual Meeting of the American Society of Hematology; December 5-8, 2020. Abstract 1419.
  9. Trudel S, McCurdy A, Sutherland HJ, et al. Part 1 results of a dose-finding study of belantamab mafodotin in combination with pomalidomide and dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM). Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 1653.
  10. Dimopoulos A, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomized, phase 3 trial. Lancet Oncol. 2021;22:801-812.
  11. Usmani SZ, Alonso A, Quach H, et al. DREAMM-9: phase I study of belantamab mafodotin plus standard of care in patients with transplant-ineligible newly diagnosed multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 2738.
  12. Callander NS, Ribrag V, Richardson PG, et al. DREAMM-5 study: investigating the synergetic effects of belantamab mafodotin plus inducible T-cell co-stimulator agonist (aICOS) combination therapy in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 897.
  13. Munshi NC, Anderson LD Jr, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384:705-716.
  14. Anderson LD, Munshi NC, Shah N, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: Updated KarMMa results. Presented at: 57th Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 8016.
  15. 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 (CARTITUDE-1): a phase 1b/2 open-label study [published correction appears in Lancet. 2021 Oct 2;398:1216]. Lancet. 2021;398:314-324.
  16. Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 549.
  17. Zhao WH, Liu J, Wang BY, et al. A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. J Hematol Oncol. 2018;11:141.
  18. Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. Presented at: 57th Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 8005.
  19. Raje NS, Shah N, Jagannath S, et al. Updated clinical and correlative results from the phase I CRB-402 study of the BCMA-targeted CAR T Cell therapy bb21217 in patients with relapsed and refractory multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 548.
  20. Kumar SK, Baz RC, Orlowski RZ, et al. Results from Lummicar-2: a phase 1b/2 study of fully human B-cell maturation antigen-specific CAR T cells (CT053) in patients with relapsed and/or refractory multiple myeloma. 2020;136(suppl 1):133.
  21. Costello CL, Derman BA, Kocoglu MH, et al. Clinical trials of BCMA-targeted CAR-T cells utilizing a novel non-viral transposon system. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 3858.
  22. Jiang H, Dong B, Gao L, et al. Long-term follow-up results of a multicenter first-in-human study of the dual BCMA/CD19 Targeted FasT CAR-T GC012F for patients with relapsed/refractory multiple myeloma. Presented at: 57th Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 8014.
  23. Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematol Oncol. 2019;37(suppl 1):48-52.
  24. van de Donk NWCJ, Themeli M, Usmani SZ. Determinants of response and mechanisms of resistance of CAR T-cell therapy in multiple myeloma. Blood Cancer Discov. 2021;2:302-318.
  25. Doan A, Pulsipher MA. Hypogammaglobulinemia due to CAR T-cell therapy. Pediatr Blood Cancer. 2018;65:10.1002/pbc.26914.
  26. Coronavirus (COVID-19) update: FDA authorizes new long-acting monoclonal antibodies for pre-exposure prevention of COVID-19 in certain individuals. December 2021. Available at: fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-new-long-acting-monoclonal-antibodies-pre-exposure. Accessed March 13, 2022.
  27. Stewart AG, Henden AS. Infectious complications of CAR T-cell therapy: a clinical update. Ther Adv Infect Dis. 2021;8:20499361211036773.
  28. Kennedy VE, Wong C, Huang CY, et al. Macrophage activation syndrome-like manifestations (MAS-L) following BCMA-directed CAR T-cells in multiple myeloma. Blood. 2020;136(suppl 1):7-8.
  29. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-638.
  30. 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;380:1726-1737.
  31. Hyrenius-Wittsten A, Roybal KT. Paving new roads for CARs. Trends Cancer. 2019;5:583-592.
  32. Zhao J, Lin Q, Song Y, Liu D. Universal CARs, universal T cells, and universal CAR T cells. J Hematol Oncol. 2018;11:132.
  33. Moghimi B, Muthugounder S, Jambon S, et al. Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma. Nat Commun. 2021;12:511.
  34. Shah N, Alsina M, Siegel D, et al. Initial results from a phase I clinical study of bb21217, a next-generation anti-BCMA CAR T cell therapy. Blood. 2018;132(suppl 1):488.
  35. Usmani SZ, Garfall AL, van de Donk NWCJ, et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021;398:665-674.
  36. Moreau P, Usmani SZ, Garfall AL, et al. Updated results from MajesTEC-1: phase 1/2 study of teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in relapsed/refractory multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 896.
  37. Bahlis NJ, Raje NS, Costello C, et al. Efficacy and safety of elranatamab (PF-06863135), a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MM). Presented at: 57th Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract
  38. Kumar SK, D’Souza A, Shah N, et al. A phase 1 first-in-human study of Tnb-383B, a BCMA x CD3 bispecific T-cell redirecting antibody, in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract
  39. Harrison SJ, Minnema MC, Lee HC, et al. A phase 1 first in human (FIH) study of AMG 701, an anti-B-cell maturation antigen (BCMA) half-life extended (HLE) BiTE (bispecific T-cell engager) molecule, in relapsed/refractory (RR) multiple myeloma (MM). Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract 181.
  40. Rodriguez-Otero P, Dholaria B, Askari E, et al. Subcutaneous teclistamab in combination with daratumumab for the treatment of patients with relapsed/refractory multiple myeloma: results from a phase 1b multicohort study. Presented at: 63rd Annual Meeting of the American Society of Hematology; December 11-14, 2021. Abstract
  41. Daratumumab [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2022.
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