Skip to main content

Advertisement

SpringerLink
Log in

Targeting BCMA in Multiple Myeloma

  • Multiple Myeloma (P Kapoor, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Despite considerable advances in the treatment of multiple myeloma (MM) in the last decade, a significant number of patients still progress on current available therapies. Here, we review treatment modalities used to target BCMA in the treatment of MM, specifically antibody-drug conjugates (ADC), bispecific antibody constructs, and chimeric antibody receptor (CAR) modified T-cell therapies. We will provide an overview of therapies from these classes that have presented or published clinical data, as well as data on mechanisms of resistance to these novel agents.

Recent Findings

Clinical trials exploring different BCMA-targeting modalities to treat multiple myeloma are underway and demonstrate promising results. In relapsed/refractory multiple myeloma, anti-BCMA ADCs and bispecific antibody constructs are showing impressive efficacy with manageable side effect profiles. In parallel, adoptive cellular therapy has induced dramatic durable responses in multiply relapsed and refractory myeloma patients.

Summary

Therapeutic approaches targeting BCMA hold significant potential in the management of multiple myeloma and will soon be incorporated in combination with current standard therapies to improve outcomes for patients with multiple myeloma. In addition, novel approaches are being evaluated to overcome resistance mechanisms to anti-BCMA therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30.

    Article  PubMed  Google Scholar 

  2. Durie BG, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389(10068):519–27.

    Article  PubMed  CAS  Google Scholar 

  3. Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111(5):2516–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Goldschmidt H, Lokhorst HM, Mai EK, van der Holt B, Blau IW, Zweegman S, Weisel KC, Vellenga E, Pfreundschuh M, Kersten MJ, Scheid C, Croockewit S, Raymakers R, Hose D, Potamianou A, Jauch A, Hillengass J, Stevens-Kroef M, Raab MS, et al. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMG-HD4 trial. Leukemia. 2018;32(2):383–90.

    Article  PubMed  CAS  Google Scholar 

  5. Shah UA, Mailankody S. Emerging immunotherapies in multiple myeloma. BMJ. 2020;370:m3176.

    Article  PubMed  Google Scholar 

  6. Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, Gupta R, Varnado W, Fiala MA, Chhabra S, Malek E, Mansour J, Paul B, Barnstead A, Kodali S, Neppalli A, Liedtke M, Narayana S, Godby KN, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. 2019;33(9):2266–75.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kumar SK, Therneau TM, Gertz MA, Lacy MQ, Dispenzieri A, Rajkumar SV, Fonseca R, Witzig TE, Lust JA, Larson DR, Kyle RA, Greipp PR. Clinical course of patients with relapsed multiple myeloma. Mayo Clin Proc. 2004;79(7):867–74.

    Article  PubMed  CAS  Google Scholar 

  8. Madry C, Laabi Y, Callebaut I, Roussel J, Hatzoglou A, Le Coniat M, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  9. Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, Yellin O, Nichols CM, Dreyer MP, Ahles CP, Robinson A, Madden E, Waterman GN, Swift RA, Bonavida B, Boccia R, Vescio RA, Crowley J, Chen H, Berenson JR. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012;158(6):727–38.

    Article  PubMed  CAS  Google Scholar 

  10. Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7(11):1187–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, Gross JA, Greipp PR, Jelinek DF. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689–94.

    Article  PubMed  CAS  Google Scholar 

  12. O'Connor BP, Raman VS, Erickson LD, Cook WJ, Weaver LK, Ahonen C, Lin LL, Mantchev GT, Bram RJ, Noelle RJ. BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med. 2004;199(1):91–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, Fieles WE, Tunstead J, McCahon L, Germaschewski FM, Mayes PA, Craigen JL, Rodriguez-Justo M, Yong KL. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016;174(6):911–22.

    Article  PubMed  CAS  Google Scholar 

  14. Tai YT, Acharya C, An G, Moschetta M, Zhong MY, Feng X, Cea M, Cagnetta A, Wen K, van Eenennaam H, van Elsas A, Qiu L, Richardson P, Munshi N, Anderson KC. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127(25):3225–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Sanchez E, Gillespie A, Tang G, Ferros M, Harutyunyan NM, Vardanyan S, Gottlieb J, Li M, Wang CS, Chen H, Berenson JR. Soluble B-cell maturation antigen mediates tumor-induced immune deficiency in multiple myeloma. Clin Cancer Res. 2016;22(13):3383–97.

    Article  PubMed  CAS  Google Scholar 

  16. Ghermezi M, Li M, Vardanyan S, Harutyunyan NM, Gottlieb J, Berenson A, Spektor TM, Andreu-Vieyra C, Petraki S, Sanchez E, Udd K, Wang CS, Swift RA, Chen H, Berenson JR. Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients. Haematologica. 2017;102(4):785–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, Craigen J, Yates J, Gliddon L, Fieles W, Hoang B, Tunstead J, Christie AL, Kung AL, Richardson P, Munshi NC, Anderson KC. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123(20):3128–38.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Kinneer K, Flynn M, Thomas SB, Meekin J, Varkey R, Xiao X, Zhong H, Breen S, Hynes PG, Fleming R, Bezabeh B, Chen C(T), Wetzel L, Chen R, Dimasi N, Tai YT, Anderson KC, Herbst R, Howard PW, et al. Preclinical assessment of an antibody-PBD conjugate that targets BCMA on multiple myeloma and myeloma progenitor cells. Leukemia. 2019;33(3):766–71.

    Article  PubMed  Google Scholar 

  19. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Anderson LD Jr, Sutherland HJ, Yong K, Hoos A, Gorczyca MM, Lahiri S, He Z, Austin DJ, Opalinska JB, Cohen AD. Targeting B-cell maturation antigen with GSK2857916 antibody-drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018;19(12):1641–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21(2):207–21 A potentially practice changing phase 2 study leading to the FDA approval of the first anti-BCMA directed therapy, belantamab mafodotin.

    Article  PubMed  CAS  Google Scholar 

  21. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD. Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019;9(4):37.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Pivotal DREAMM-2 study: Single-agent belantamab mafodotin (GSK2857916) in patients with relapsed/refractory multiple myeloma (RRMM) refractory to proteasome inhibitors (PIs), immunomodulatory agents, and refractory and/or intolerant to anti-CD38 monoclonal antibodies (mAbs). J Clin Oncol. 2020;38(15_suppl):8536

  23. Trudel S, McCurdy A, Sutherland HJ, Louzada ML, Venner CP, White DJ, et al. Part 1 results of a dose finding study of belantamab mafodotin (GSK2857916) in combination with pomalidomide (POM) and dexamethasone (DEX) for the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). Blood. 2020;136(Supplement 1):17–8.

  24. Popat R, Nooka A, Stockerl-Goldstein K, Abonour R, Ramaekers R, Khot A, 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). Blood. 2020;136(Supplement 1):19–20.

    Article  Google Scholar 

  25. Kumar SK, Migkou M, Bhutani M, Spencer A, Ailawadhi S, Kalff A, et al. Phase 1, First-in-Human Study of MEDI2228, a BCMA-targeted ADC in patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):26–7.

    Article  Google Scholar 

  26. Huehls AM, Coupet TA, Sentman CL. Bispecific T-cell engagers for cancer immunotherapy. Immunol Cell Biol. 2015;93(3):290–6.

    Article  PubMed  CAS  Google Scholar 

  27. Velasquez MP, Bonifant CL, Gottschalk S. Redirecting T cells to hematological malignancies with bispecific antibodies. Blood. 2018;131(1):30–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Labrijn AF, Meesters JI, Priem P, de Jong RN, van den Bremer ET, van Kampen MD, et al. Controlled Fab-arm exchange for the generation of stable bispecific IgG1. Nat Protoc. 2014;9(10):2450–63.

    Article  PubMed  CAS  Google Scholar 

  29. Labrijn AF, Meesters JI, de Goeij BE, van den Bremer ET, Neijssen J, van Kampen MD, et al. Efficient generation of stable bispecific IgG1 by controlled Fab-arm exchange. Proc Natl Acad Sci U S A. 2013;110(13):5145–50.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gramer MJ, van den Bremer ET, van Kampen MD, Kundu A, Kopfmann P, Etter E, et al. Production of stable bispecific IgG1 by controlled Fab-arm exchange: scalability from bench to large-scale manufacturing by application of standard approaches. MAbs. 2013;5(6):962–73.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Topp MS, Duell J, Zugmaier G, Attal M, Moreau P, Langer C, et al. Anti-B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma. J Clin Oncol. 2020;38(8):775–83 A proof-of-concept study for the efficacy of anti-BCMA BiTE therapy in multiple myeloma.

    Article  PubMed  CAS  Google Scholar 

  32. Harrison SJ, Minnema MC, Lee HC, Spencer A, Kapoor P, Madduri D, 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). Blood. 2020, 136(Supplement 1):28–9.

  33. Panowski SH, Kuo T, Chen A, Geng T, van Blarcom TJ, Lindquist K, Chen W, Chaparro-Riggers J, Sasu B. Preclinical evaluation of a potent anti-BCMA CD3 bispecific molecule for the treatment of multiple myeloma. Blood. 2016;128(22):383.

    Article  Google Scholar 

  34. Raje NS, Andrzej J, Gasparetto C, Cornell RF, Krupka HI, Navarro D, et al. Safety, Clinical activity, pharmacokinetics, and pharmacodynamics from a phase I study of PF-06863135, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2019;134(Supplement_1):1869.

    Article  Google Scholar 

  35. Lesokhin AM, Levy MY, Dalovisio AP, Bahlis N, Solh M, Sebag M, et al. Preliminary safety, efficacy, pharmacokinetics, and pharmacodynamics of subcutaneously (SC) administered PF-06863135, a b-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(Supplement 1):8–9.

    Article  Google Scholar 

  36. Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, Lipp S, Merino J, Prosper F, Emde M, Delon C, Latzko M, Gianotti R, Lüoend R, Murr R, Hosse RJ, Harnisch LJ, Bacac M, Fauti T, 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.

    Article  PubMed  CAS  Google Scholar 

  37. Costa LJ, Wong SW, Bermudez A, de la Rubia J, Mateos M-V, Ocio EM, et al. First clinical study of the B-cell maturation antigen (BCMA) 2+1 T cell engager (TCE) CC-93269 in patients (Pts) with relapsed/refractory multiple myeloma (RRMM): interim results of a phase 1 multicenter trial. Blood. 2019;134(Supplement_1):143.

    Article  Google Scholar 

  38. Pillarisetti K, Powers G, Luistro L, Babich A, Baldwin E, Li Y, Zhang X, Mendonça M, Majewski N, Nanjunda R, Chin D, Packman K, Elsayed Y, Attar R, Gaudet F. Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma. Blood Adv. 2020;4(18):4538–49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Frerichs KA, Broekmans MEC, Marin Soto JA, van Kessel B, Heymans MW, Holthof LC, Verkleij CPM, Boominathan R, Vaidya B, Sendecki J, Axel A, Gaudet F, Pillarisetti K, Zweegman S, Adams HC III, Mutis T, van de Donk NWCJ. Preclinical Activity of JNJ-7957, a Novel BCMA×CD3 Bispecific Antibody for the Treatment of Multiple Myeloma, Is Potentiated by Daratumumab. Clin Cancer Res. 2020;26(9):2203–15.

    Article  PubMed  CAS  Google Scholar 

  40. Usmani SZ, Mateos M-V, Nahi H, Krishnan AY, Donk NWCJvd, Miguel JS, et al. Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM). J Clin Oncol. 2020;38(15_suppl):100.

  41. Garfall AL, Usmani SZ, Mateos M-V, Nahi H, van de Donk NWCJ, San-Miguel JF, et al. Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed and/or refractory multiple myeloma (RRMM). Blood. 2020;136(Supplement 1):27.

    Article  Google Scholar 

  42. Madduri D, Rosko A, Brayer J, Zonder J, Bensinger WI, Li J, et al. REGN5458, a BCMA x CD3 bispecific monoclonal antibody, induces deep and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). Blood. 2020;136(Supplement 1):41–2.

    Article  Google Scholar 

  43. Rodriguez C, D'Souza A, Shah N, Voorhees PM, Buelow B, Vij R, et al. Initial results of a phase I study of TNB-383B, a BCMA x CD3 bispecific T-cell redirecting antibody, in relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):43–4.

    Article  Google Scholar 

  44. Mikkilineni L, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood. 2017;130(24):2594–602.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ghosh A, Mailankody S, Giralt SA, Landgren CO, Smith EL, Brentjens RJ. CAR T cell therapy for multiple myeloma: where are we now and where are we headed? Leuk Lymphoma. 2018;59(9):2056–67.

    Article  PubMed  CAS  Google Scholar 

  46. Ma T, Shi J, Liu H. Chimeric antigen receptor T cell targeting B cell maturation antigen immunotherapy is promising for multiple myeloma. Ann Hematol. 2019;98(4):813–22.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Shah UA, Smith EL. Multiple myeloma, targeting B-cell maturation antigen with chimeric antigen receptor T-cells. Cancer J. 2019;25(3):208–16.

    Article  PubMed  CAS  Google Scholar 

  48. Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Turka A, Lam LP, Morgan RA, Friedman K, Massaro M, Wang J, Russotti G, Yang Z, Campbell T, Hege K, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380(18):1726–37.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Lin Y, Raje NS, Berdeja JG, Siegel DS, Jagannath S, Madduri D, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in patients with relapsed and refractory multiple myeloma: updated results from phase 1 CRB-401 study. Blood. 2020;136(Supplement 1):26–7.

    Google Scholar 

  50. Munshi NC, Anderson LD, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–16 A phase 2 study of ide-cel in heavily pretreated RRMM patients demonstrating benefit of anti-BCMA CAR T cell therapy with durable responses leading to the FDA approval of the first CAR T cell therapy for multiple myeloma.

    Article  PubMed  CAS  Google Scholar 

  51. Alsina M, Shah N, Raje NS, Jagannath S, Madduri D, Kaufman JL, et al. Updated results from the phase I CRB-402 study of anti-Bcma CAR-T cell therapy bb21217 in patients with relapsed and refractory multiple myeloma: correlation of expansion and duration of response with T cell phenotypes. Blood. 2020;136(Supplement 1):25–6.

    Article  Google Scholar 

  52. Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, Zhang YL, Wang FX, Zhang PY, Lei B, Gu LF, Wang JL, Yang N, Zhang R, Zhang H, Shen Y, Bai J, Xu Y, Wang XG, 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(1):141.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Wang B-Y, Zhao W-H, Liu J, Chen Y-X, Cao X-M, Yang Y, et al. Long-term follow-up of a phase 1, first-in-human open-label study of LCAR-B38M, a structurally differentiated chimeric antigen receptor T (CAR-T) cell therapy targeting B-cell maturation antigen (BCMA), in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Blood. 2019;134(Supplement_1):579.

    Article  Google Scholar 

  54. Madduri D, Berdeja JG, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, et al. CARTITUDE-1: phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):22–5 A phase 1b/2 study of cilta-cel in heavily pretreated RRMM patients demonstrating impressive overal response rates and survival benefit.

    Article  Google Scholar 

  55. Mailankody S, Htut M, Lee KP, Bensinger W, Devries T, Piasecki J, et al. JCARH125, anti-BCMA CAR T-cell therapy for relapsed/refractory multiple myeloma: initial proof of concept results from a phase 1/2 multicenter study (EVOLVE). Blood. 2018;132(Supplement 1):957.

    Article  Google Scholar 

  56. Mailankody S, Jakubowiak AJ, Htut M, Costa LJ, Lee K, Ganguly S, et al. Orvacabtagene autoleucel (orva-cel), a B-cell maturation antigen (BCMA)-directed CAR T cell therapy for patients (pts) with relapsed/refractory multiple myeloma (RRMM): update of the phase 1/2 EVOLVE study (NCT03430011). J Clin Oncol. 2020;38(15_suppl):8504. A phase 1/2 study of orva-cel in heavily pretreated RRMM patients demonstrating impressive overal response rates and survival benefit.

  57. Hao S, Jin J, Jiang S, Li Z, Zhang W, Yang M, et al. Two-year follow-up of investigator-initiated phase 1 trials of the safety and efficacy of fully human anti-Bcma CAR T Cells (CT053) in relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):27–8.

    Article  Google Scholar 

  58. Kumar SK, Baz RC, Orlowski RZ, Anderson LD Jr, Ma H, Shrewsbury A, 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. Blood. 2020;136(Supplement 1):28–9.

    Article  Google Scholar 

  59. Gregory T, Cohen AD, Costello CL, Ali SA, Berjeda JG, Ostertag EM, et al. Efficacy and safety of P-BCMA-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM). Blood. 2018;132(Supplement 1):1012.

    Article  Google Scholar 

  60. Costello CL, Cohen AD, Patel KK, Ali SS, Berdeja JG, Shah N, et al. Phase 1/2 study of the safety and response of P-BCMA-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM) (PRIME) with novel therapeutic strategies. Blood. 2020, 136(Supplement 1):29–30.

  61. Mailankody S, Matous JV, Liedtke M, Sidana S, Malik S, Nath R, et al. Universal: an allogeneic first-in-human study of the anti-Bcma ALLO-715 and the anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):24–5 A phase 1 study of ALLO-715, an allogeneic ("off-the-shelf") CAR T cell therapy, in RRMM, showing feasibility, safety and efficacy.

    Article  Google Scholar 

  62. Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, Stetler-Stevenson M, Salem D, Yuan C, Pavletic S, Kanakry JA, Ali SA, Mikkilineni L, Feldman SA, Stroncek DF, Hansen BG, Lawrence J, Patel R, Hakim F, et al. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36(22):2267–80.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, Vogl DT, Weiss BM, Dengel K, Nelson A, Plesa G, Chen F, Davis MM, Hwang WT, Young RM, Brogdon JL, Isaacs R, Pruteanu-Malinici I, Siegel DL, et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019;129(6):2210–21.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Munshi NC, Larry D. Anderson J, Shah N, Jagannath S, Berdeja JG, Lonial S, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results. J Clin Oncol. 2020;38(15_suppl):8503.

  65. Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF, Xu J, Zhuang Y, Zhang W, Weng XQ, Wu J, Wang Y, Wang J, Yan H, Xu WB, Jiang H, du J, Ding XY, Li B, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci U S A. 2019;116(19):9543–51.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Lam N, Trinklein ND, Buelow B, Patterson GH, Ojha N, Kochenderfer JN. Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains. Nat Commun. 2020;11(1):283.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Kotani H, Li G, Yao J, Mesa TE, Chen J, Boucher JC, et al. Aged CAR T cells exhibit enhanced cytotoxicity and effector function but shorter persistence and less memory-like phenotypes. Blood. 2018;132(Supplement 1):2047.

    Article  Google Scholar 

  68. Chen H, Li M, Xu N, Ng N, Sanchez E, Soof CM, Patil S, Udd K, Bujarski S, Cao J, Hekmati T, Ghermezi M, Zhou M, Wang EY, Tanenbaum EJ, Zahab B, Schlossberg R, Yashar MA, Wang CS, et al. Serum B-cell maturation antigen (BCMA) reduces binding of anti-BCMA antibody to multiple myeloma cells. Leuk Res. 2019;81:62–6.

    Article  PubMed  CAS  Google Scholar 

  69. Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019;16(6):372–85.

    PubMed  PubMed Central  CAS  Google Scholar 

  70. Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B, Shalabi H, Fountaine TJ, Shern JF, Majzner RG, Stroncek DF, Sabatino M, Feng Y, Dimitrov DS, Zhang L, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24(1):20–8.

    Article  PubMed  CAS  Google Scholar 

  71. Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, Hudecek M, Comstock ML, Rajan A, Patel BKR, Voutsinas JM, Wu Q, Liu L, Cowan AJ, Wood BL, Green DJ, Riddell SR. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134(19):1585–97.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Cowan AJ, Pont M, Sather BD, Turtle CJ, Till BG, Nagengast AM, et al. Efficacy and safety of full human BCMA CAR T cells in combination with a gamma secretase inhibitor to increase BCMA surface expression in patients with relapsed or refractory multiple myeloma. Blood. 2019;134(Supplement_1):204.

    Article  Google Scholar 

  73. Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai Y-T, Prabhala R, et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun. 2021;12(868).

  74. Shah UA, Mailankody S. CAR T and CAR NK cells in multiple myeloma: Expanding the targets. Best Pract Res ClinHaemat. 2020;33(1):101141.

  75. Jiang H, Dong B, Gao L, Liu L, Ge J, He A, et al. Clinical results of a multicenter study of the first-in-human dual BCMA and CD19 targeted novel platform fast CAR-T cell therapy for patients with relapsed/refractory multiple myeloma. Blood. 2020;136(Supplement 1):25–6.

    Google Scholar 

  76. Lee L, Draper B, Chaplin N, Philip B, Chin M, Galas-Filipowicz D, Onuoha S, Thomas S, Baldan V, Bughda R, Maciocia P, Kokalaki E, Neves MP, Patel D, Rodriguez-Justo M, Francis J, Yong K, Pule M. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018;131(7):746–58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Fernández de Larrea C, Staehr M, Lopez AV, Ng KY, Chen Y, Godfrey WD, Purdon TJ, Ponomarev V, Wendel HG, Brentjens RJ, Smith EL. Defining an optimal dual-targeted CAR T-cell therapy approach simultaneously targeting BCMA and GPRC5D to prevent BCMA escape–driven relapse in multiple myeloma. Blood Cancer Discov. 2020;1(2):146–54.

    Article  PubMed Central  PubMed  Google Scholar 

  78. Yan Z, Cao J, Cheng H, Qiao J, Zhang H, Wang Y, Shi M, Lan J, Fei X, Jin L, Jing G, Sang W, Zhu F, Chen W, Wu Q, Yao Y, Wang G, Zhao J, Zheng J, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol. 2019;6(10):e521–e9.

    Article  PubMed  Google Scholar 

  79. Cohen AD, Garfall AL, Dogan A, Lacey SF, Martin C, Lendvai N, Vogl DT, Spear M, Lesokhin AM. Serial treatment of relapsed/refractory multiple myeloma with different BCMA-targeting therapies. Blood Adv. 2019;3(16):2487–90.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Funding support for this publication was provided by the Memorial Sloan Kettering NIH/NCI Cancer Center Support Grant (P30 CA008748) and Parker Institute for Cancer Immunotherapy (U.A.S.).

Author information

Authors and Affiliations

  1. Myeloma Service Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th Street, New York, NY, 10021, USA

    Carlyn Rose Tan & Urvi A. Shah

Authors
  1. Carlyn Rose Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Urvi A. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlyn Rose Tan.

Ethics declarations

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

Carlyn Rose Tan has financial interests in Janssen as a result of an immediate family member’s employment. Urvi A. Shah has received research funding from Celgene/Bristol Myers Squibb, Janssen, and Parker Institute for Cancer Immunotherapy to her institution and honorariums for continuing medical education activity from the Physicians Education Resource, all outside of the submitted work.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Multiple Myeloma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, C.R., Shah, U.A. Targeting BCMA in Multiple Myeloma. Curr Hematol Malig Rep 16, 367–383 (2021). https://doi.org/10.1007/s11899-021-00639-z

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-021-00639-z

Keywords

Search

Navigation