CHIMERIC ANTIGEN RECEPTOR T CELLS FOR THE TREATMENT OF MULTIPLE MYELOMA CAR T Cells and Myeloma Treatment

Main Article Content

Ugo Testa
Elvira Pelosi
Dr. Germana Castelli

Keywords

Myeloma, CAR T Cells

Abstract

Multiple myeloma (MM), characterized by abnormal proliferation of clonal plasma cells, is an incurable hematological malignancy. Various immunotherapy strategies have emerged as an efficacious approach for the treatment of MM, including monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, and chimeric antigen receptor T (CAR-T) cells. Anti-B-cell maturation antigen (BCMA) CAR-T cells have revolutionized the treatment of MM patients with relapsed/refractory disease and their clinical use was approved for the treatment of these patients.


Despite this progress, the efficacy of CAR-T cells in MM is limited by the responsiveness of only a part of the treated patients, the relapse of other patients, the cost of the treatment and the diminished response in patients with prior exposure to anti-BCMA targeting agents. Ongoing clinical trials are evaluating the use of CAR-T cells at an earlier stage of MM disease and the use of CAR-T cells targeting other membrane antigens expressed on malignant plasma cells.

Downloads

Download data is not yet available.


Abstract 602
PDF Downloads 191
HTML Downloads 38

References

1) Eshhar Z, Waks T, Gross G, Schindler DG, Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA 1993; 90: 720-724.
2) Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, Kamble RT, Bollard CM, Gee AP, Mei Z, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest 2011; 121: 1822-1826.
3) Ceya MA, Khericha M, Harris CM, Puig-Saus C, Chen YY. CAR-T cell manufacturing: major process parameters and next-generation strategies. J Exp Med 2024; 221: e20230903.
4) Wiedmeier-Nutor JE, Bergsagel PL. Review of multiple myeloma genetics including effects on prognosis, response to treatment, and diagnostic workup. Life 2022; 12; 812.
5) Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, Liedtke M, Rosenblatt J, Maus M, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med 2019; 380: 1726-1737.
6) Lin Y, Raje NS, Bardeja JG, Siegel DS, Jaganath S, Madduri D, Liedtke M, Rosenblatt J, Maus MV, Massaro M, et al. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med 2023; 29: 2286-2294.
7) Munshi NC, Anderson LD, Shah N, Madduri N, Berdeja J, Lonial S, Raje N, Lin Y, Siegel D, Oriol A, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 2021; 384: 705-716.
8) Rodriguez-Otero P, Allawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med 2023; 388: 1002-1014.
9) Usmani S, Patel K, Hari P, Berdeja J, Alsina M, Vij R, Raje N, Leleu X, Dhodapakar M, Reshef R, et al. KarMMa-2 cohort 2a: efficacy and safety of idecabtagene vicleucel in clinical high-risk multiple myeloma patients with early relapse after frontline autologous stem cell transplantation. Blood 2021; 140 (suppl.1): 875-877.
10) Dhodapakar M, Alsina M, Berdeja J, Patel K, Vij R, Leleu X, Truppel-Hartmann A, Basudhar D, Thompson E, Zheng X, et al. KarMMa-2 cohort 2c: efficacy anf safety of idecabtagene vicleucel in patients with clinical high-risk multiple myeloma due to inadequate response to frontline autologous stem cell transplantation. Blood 2022; 14 (suppl.1): 7441-7443.
11) Hansen DK, Sidana S, Peres LC, Leitzinger CC, Shune L, Shrewsbury A, Gonzalez R, Sborov DW, Wagner C, Dima D, et al. Idecabtagene vivleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol 2023; 41: 2087-2097.
12) Cayla S, Ferment B, Bigot N, Caillot D, Lafon I, Karlin L, Lazareth A, Touzeau C, Leleu X, Moya N, et al. French early natiowide idecabtagene vicleucel (Ide-Cel) chimeric antigen receptor (CAR) T-cell therapy experience in patients with relapsed/refractory multiple/myeloma (FENIX): update of the IFM study from the Descar-T registry. Blood 2023; 142( suppl.1): 2139.
13) Sidana S, Ahmed N, Akhtar OS, Heim M, Brazauyskas R, Hansen DK, Ferreri C, Freeman CL, Afrough A, et al. Rel world outcomes with idecabtagene vicleucel (Ide-Cel) CAR-T cell therapy for relapsed/refractory multiple myeloma. Blood 2023; 142 (suppl.1): 705.
14) Pasvolsky O, Hildebrandt M, Subramanian N, Ferreri C, Lee H, Manasanch EE, Thomas SK, Weber DM, Gaballa M, Dilalrd C, et al. Safety and efficacy outcomes for patients with high-risk multiple myeloma receiving idecabtagene vicleucel: the MD Anderson experience. Blood 2023; 142 (suppl.1): 4712.
15) Plasecki J, Desai K, Courtney C, Thompson E, Pratt J, Raje NS, Patel KK, Raab MS, Cook M, Simonsen KL, et al. Baseline and early post-infusion biomarkers associated with optimal response to idecabtagene cicleucel (Ide-cel) in the KarMMa-3 study at triple-class-exposed (TCE) relapsed and refractory multiple myeloma (RRMM). J Clin Oncol 2023; 41(suppl. 16): 8031.
16) Pan DD, Mouhieddine TH, Fu W, Moshier E, Parekh S, Jagannath S, Rossi AC, Cho HJ, Richter J, Sanchez LJ, et al. Inflammatory biomarkers and outcomes in multiple myeloma patients after CAR T-cell therapy. Blood 2023; 142 (suppl.1): 92.
17) Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, Stewart AK, Hari P, Htut M, Lesokhin A, 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. Lancet 2021; 398: 314-324.
18) Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, Avigan D, Deol A, Htut M, Lesokhin A, et al. Ciltacabtagene autoleucel, an anti-B-cxell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol 2023; 41: 1265-1274.
19) Lin Y, Martin T, Usmani SZ, Berdeja J, Jakubawiak A, Agha M, Cohen A, Deol O, Htut M, Lesakhin A, Munshi N, et al. MM-309 CARTITUDE-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leukemia 2023; 23 (suppl.1): 5488-5489.
20) Cohen AD, Parewkh S, Santomasso BD, Perez-Larraya JC, van de Donk N, Arnulf B, Mateos MV, Lendvai N, Jackson CC, Braganca K, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J 2022; 12: 32.
21) Htut M, Cohen AD, Martin T, Berdeja JG, Usmani SZ, Agha M, Jackson CC, Madduri D, Deraedt W, Zudaire E, et al. Ciltacabtagene autoleucel in patients with prior allogeneic stem cell transplant in the CARTITUDE-1 study. Clin Lymphoma Myeloma Leuk 2023; S2152.
22) Martin T, Agha M, Cohen AD, Htut M, Stewart AK, Hari P, Berdejs JG, Usmani SZ, Yeh TM, Olyslager Y, et al. Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study. Lancet Hematol 2022; 9: e897-e905.
23) Mateos MV, Weisel K, Martin T, Berdeja JG, Jakubowiak A, Stewart AK, Jagannath S, Lin Y, Diels J, Ghilotti F, et al. Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice. Haematologica 2023; 108: 2192-2202.
24) Montes de Oca R, Gu J, Zhao H, Zelinsky K, Wu D, Davis C, Patel J, Foulk B, Boominathan R, Lau O, et al. Biomarker correlates of response to ciltacabtagene autoleucel in patients with relapsed or refractory multiple myeloma from CARTITUDE-1, a phase 1b/2 open-label study, al the 3-year follow-up. Blood 2023; 142 (suppl.1): 2099.
25) Cohen EH, Delforge M, Hillengass J, Goldschmidt H, Weisel K, Raab MS, Scheid C, Schecter JM, De Braganca KC, Varsos K, et al. CARTITUDE-2 update: ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1-3 prior lines of therapy. Hema-Sphere 2022; 6 (suppl.2): P08.
26) Van de Donk N, Agha ME, Cohen AD, Cohen YC, Anguille S, Kerra T, Roeloffzen W, Scehter JM, De Braganca KC, Varsos H, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy. CARTITUDE-2, cohort B. J Clin Oncol 2022; 40 (suppl. 16): 8029.
27) Hillengass J, Cohen AD, Agha ME, Delforge M, Kerre T, Roeloffzen W, Einsele H, Goldschmidt H, Weisel K, Raab MS, et al. the phase 2 CARTITUDE-2 trial updated efficacy amd safety of ciltacabtagene autoleucel in patients with multiple myeloma and 1-3 prior lines of therapy (cohort A) and with early relapse after first line treatment (cohort B). Blood 2023; 142 (suppl.1): 1021.
28) Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Pavia B, van de Donk N, Martin T, Suvannsankha A, De Braganca KC, Corsale C, et al. Efficay and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood 2023; 141: 219-230.
29) San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, de Larrea CF, Matinez-Lopez J, Moreau P, Touzeau C, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med 2023; 389: 335-347.
30) Sidiqi MH, Corradini P, Putill D, Einsele H, Dhakal B, Karlin L, Manier S, Lida S, Giebel S, Harrison SJ, Lipe B, et al. Efficay and safety in patients with lenalidomide-refractory multiple myeloma after 1-3 prior lines who received a single infusion of ciltacabtagene autoleucel as study treatment in the phase 3 CARTITUDE-4 trial. Blood 2023; 142 (suppl.1): 4866.
31) Martin T, Usmani SZ, Schecter JM, Roccia T, Jackson CC, Deraedt W, Yeh T, Usmani SZ, Pacaud L, Garrett A, et al. Updated results from a matching-adjusted indirect comparison of efficacy for celticabtagene autoleucel in CARTITUDE-1 versus idecabtagene vivleuycel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin 2023; 39: 81-89.
32) Bar N, Diels J, van Sanden S, Mendes J, Hernando T, Cost P, Schecter JM, Lendvai N, Patel N, Ishioda T, et al. Comparative efficacy of ciltacabtagene autoleucel versus idacabtagene vicleucel in the treatment of patients with relapsed or refractory multiple myeloma previously treated with 2-4 prior lines of therapy using a matching-sdjusted indirect comparison. Blood 2023; 142(suppl.1): 2141.
33) Xu J, Wang BY, Yu SH, Chen SJ, Yang SS, Liu R, Chen LJ, Hou J, Chen Z, Zhao WH, et al. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-yeaer follow-up of the LEGAND-2 trial. J Hematol Oncol 2024; 17: 23.
34) Chen D, Zhu Y, Chen Z, Jiang S, He H, Qiang W, Xiang F, Sun X, Du J. A 5-year follow-up clinical study of the B-cell maturation antigen chimeric antigen receptor T-cell therapy HDS269B in patients with relapsed or refractory multiple myeloma. Clin Cancer Res 2024, in press.
35) Van de Donk N, 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.
36) Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E. B cell antigen maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest 2019; 129: 2210-2221.
37) Da Vià MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, Zhou X, Danhof S, Kraus S, Chatterje M, et al. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med 2021; 27: 616-619.
38) Samur MK, Fulciniti MT, Samur AA, Bazarbachi AH, Tai YT, Prabhala R, Alonso A, Sperling AS, Campbell T, Petrocca F, 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.
39) Truger MS, Duell J, Zhou X, Heimeshoff L, Ruckdeschel A, John M, Riedel A, Huper S, Peter J, Walter W, et al. Single- and double-hit events in genes encoding immune targets before and after T cell-engaging antibody therapy in MM. Blood Adv 2021; 5: 3794-3798.
40) Samur MK, Samur AA, Corre J, Lannes R, Shah P, Anderson K, Avet-Loiseau H, Munshi N. Monoallelic deletion of BCMA is a frequent feature in multiple myeloma. Blood Adv 2023; 7: 6599-6603.
41) Lee H, Ahan S, Maity R, Leblay N, Zicheddu B, Truga M, Chojnacka M, Cirrincione A, Duarante M, Tilmont R, et al. Mechanisms of antigen escape from BCMA or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med 2023; 29: 2295-2306.
42) Samur MK, Martin N, Thompson E, Fulciniti MT, Samur AA, Kaiser S, Munshi NC. Differences in single cells between BCMA-targeting CAR T-cell therapy responders and non-responders reveals initial resistance and acquired resistance are driven by different factors. Blood 2023; 142 (suppl.1): 2106-2107.
43) Van Oekelen O, Nath K, Mouhieddine TH, Farzana T, Aleman A, Melkenoff DT, Ghodkle-Puranik Y, Shah GL, Lesokhin AL, Giralt S, et al. Interventions and outcomes of patients with multiple myeloma receiving salvage therapy after BCMA-directed CAR T therapy. Bloos 2023; 141: 756-765.
44) Sun F, Cheng Y, Wanchai V, Guo W, Mery D, Xu H, Gai D, Siegel E, Bailey C, Ashby C, et al. Bispecific BCMA/CD24 CAR-T cells control multiple myeloma growth. Nature Commun 2024; 15: 615.
45) Larson RC, Kann MC, Graham C, Mount CW, Castano AP, Lee WH, Bouffard AA, Takei HN, Almazan AJ, Scarfò I, et al. Anti-TACI single and dual targeting CAR T cells overcome BCMA antigen loss in multiple myeloma. Nat Commun 2023; 14: 7509.
46) Fischer L, Grieb N, Born P, Weiss R, Seiffert S, Boldt A, Fricke S, Franz P, Heyn S, Kubasch AS, et al. Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma. Leukemia 2024; in press.
47) Pont MJ, Hill T, Cole GO, Abbott JJ, Kelliher J, Salter AI, Hudececk M, Comstock ML, Rajan A, Patel B, et al. -secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood 2019; 134: 1585-1597.
48) Cowan AJ, Pont MJ, Sather BD, Turtle CJ, Till BG, Libby E, Coffey DG, Tuazon SA, Wood B, Gooley T, et al. Safety and efficacy of fully 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 2021; 138 (suppl.1): 551-553.
49) Cowan AJ, Pont MJ, Sather BD, Turtle CJ, Till BG, Libby E, Coffey DG, Tuazon SA, Wood B, Gooley T, et al. -secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for in dividuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial. Lancet Oncol 2023; 24: 811-822.
50) Green DJ, Pont M, Sather BD, Cowan AJ, Turtle CJ, Till BG, Nagengast M, Libby EN, Becker PS, Coffey DG, et al. Fully human Bcma targeted chimeric antigen receptor T cells administered in a defined composition demonstrate potency at low doses in advanced stage high risk multiple myeloma. Blood 2028; 132 (suppl.1): 1011.
51) Wang D, Wang J, Hu G, Wang W, Xiao Y, Cai H, Jiang L, Meng L, Yang Y, Zhou X, et al. A phase I study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma. Blood 2021; 137. 28909-2901.
52) Li C, Wang D, Yu Q, Li Z, Wang W, Hu G, Mu W, Li C, An N, Long X, et al. Long-term follow-up of fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma. Blood 2023; 142 (suppl.1): 4854.
53) Li C, Wang D, Song Y, Huang H, Li J, Chen B, Liu J, Dong Y, Hu K, Liu P, et al. CT103A, a novel fully human BCMA-targeting CAR-T cells in patients with relapsed/refractory multiple myeloma: updated results of phase 1b/2 study (FUMANBA-1). Hema Sphere 2023; 7(S3): 1627-1628.
54) Harrington K, Wu R, Hauskins C, Amin R, Long T, Chen A, Rahardjo A, Thayer C, Navvaro G, Myers M, et al. Development of JCARH125: optimization of a fully human anti-Bcma CAR for use in the treatment of multiple myeloma. Blood 2017; 130 (suppl.1): 1813.
55) Costa LJ, Kumar SK, Atrash S, Liedtke M, Kaur G, Derman BA, Bergsagel PL, Mailankody S, McCarthy PL, Limones J, et al. Results from the first phase I clinical study of the B-cell maturation antigen (BCMA) nex T chimeric antigen receptor (CAR) T cell therapy CC-98633/BMS-986354 in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Blood 2022; 140 (suppl.1): 1360-1362.
56) Sperling AS, Nikiforow S, Deman B, Nadeem O, Mo C, Laubach J, Anderson K, Alonso A; Im SY, Ikgawa S, et al. Phase I study data update of PHE885, a fully human BCMA-directed CAR-T cell therapy manufactured using the T-chargeTM platform for patients with relapsed/refractory (R/R) multiple myeloma (M/M). HemaSphere 2022; 6(S3): P1446.
57) Sperling AS, Derman BA, Nikiforow S, Im SY, Ikegawa S, Prabhala RH, Rodriguez DH, Li Y, Quinn DS, Pearson D, et al. Updated phase I study results of PHE885, a T-charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM). J Clin Oncol 2023; 41(suppl.16): 8004.
58) Chen W, Fu C, Fang B, Liang A, Xia Z, He Y, Lu J, Liu H, Hou M, Cai Z, et al. Phase II study of fully human BCMA-targeting CAR-T cells (Zevorcabtagene Autoleucel) in patients with relapsed/refractory multiple myeloma. Blood 2022; 140 (suppl.1) 4964-4965.
59) Fu C, Chen W, Cai Z, Yan L, Wang H, Shang J, Wu Y, Yan S, Gao W, Shi X, et al. Three-year follow-up on efficacy and safety results from phase 1 Lummicar study 1 of Zevorcabtagene Autoleucel in Chinese patients with relapsed or refractory multiple myeloma. Blood 2023; 142 (suppl.1): 4845.
60) Metelo AM, Jozwik A, Luong LA, Dominey-Foy D, Graham C, Attwood C, Inam S, Dunlop A; Sanchez K, Cuthill K, et al. Allogeneic anti-BCMA CAR T cells are superior to multiple myeloma-derived CAR T cells in preclinical studies and may be combined with gamma secretase inhibitors. Cancer Res Commun 2022; 2: 158-171.
61) Lin RJ, Nager AR, Park S, Sutton J, Lay C, Melton Z, Zhang Y, Boldajipour B, Van Blarcom TJ, Panowski SH, et al. Design and validation of inducible TurboCARs with tunable induction and combinatorial cytokine signaling. Cancer Immunol Res 2022; 10: 1069-1083.
62) Lin RJ, Sutton J, Bentley T, Vargas-Inchaustegui DA, Nguyen D, Cheng HY, Yoon H, Van Blarcom TJ, Sasu BJ, Panowski SH, et al. Constitutive turbodomains enhance expansion and antitumor activity of allogeneic BCMA CAR T cells in preclinical models. Sci Adv 2023; 9: eadg8694.
63) Mailankody S, Matous JV, Chhabra S, Liedtke M, Sidana S, Oluwole OO, Malik S, Nath R, Anwer F, Cruz JC, et al. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nat Med 2023; 29: 422-429.
64) Dholaria B, Kocoglu MH, Kin A, Asch AS, Ramakrishnan A, Bachier C, Rodriguez TE, Shune L, McArthur K McCalgue J, et al. Early results of P-BMCA-ALLO1, a fully allogeneic chimeric antigen receptor T-cell (CAR-T), in patients with relapsed/refractory multiple myeloma (RRMM). Blood 2023; 152(suppl.1): 3479.
65) Smith EL, Harrington K, Staehr M, Masakayan R, Jones J, Jong TJ, Ng KY, Ghoddusi M,Purdon TJ, Wang X, et al. GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Sci Transl Med 2019; 11: eaau7746.
66) Xia J, Li H, Yan Z, Zhou D, Wang Y, Qi Y, Cao J, Li D, Cheng H, Sang W, et al. Anti-G protein-coupled receptor, class C group 5 member D chimeric antigen receptor T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase II trial. J Clin Oncol 2023; 41: 2583-2593.
67) Zhang M, Wei G, Zhou L, Zhou J, Chen S, Zhang W, Wang D, Luo X, Cui J, Huang S, et al. GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Hematol 2023; 10: e107-e116.
68) Mailankody S, Devlin SM, Landa J, Nath K, Diamonte C, Carstens EJ, Russo D, Auclair R, Fitzgerald R, Cadzin B, et al. GPRC5D-targeted CAR T cells for myeloma. N Engl J Med 2022; 387: 1196-1206.
69) Bal S, Kocoglu MH, Nadeem O, et al. Clinical activity of BMS-986393 (CC-95266), a G protein-coupled receptor class Cgroup 5 member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T cell therapy, in pateints with relapsed and/or refractory (R/R) multiple myeloma (MM): first results from a phase 1, multicenter, open-label study. Blood 2022; 140 (suppl.1): 883-885.
70) Bal S, Htut M, Nadeem O, Anderson LD, Kocoglu H, Gregory T, Rossi AC, Martin T, Egan DN, Costa L, et al. BMS-986393 (CC-95266), a G protein -coupled receptor class C group 5 member D (GPRC5D)-targetd chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory multiple myeloma (RRMM): updated results from a phase 1 study. Blood 2023; 142 (suppl.1): 219.
71) Zhou D, Sun Q, Xia J, Gu W, Qian J, Zhuang W, Yan Z, Cheng H, Zhu F, Qi K, et al. Anti-BCMA/GPRC5D bispecific CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, single-centre, phase 1 trial. Lancet Hematol 2024; in press.
72) Garfall AL, Stadtmauer EA, Hwang WT, Lacey FV, Melenhorst JJ, Krevvata M, Carroll MP, Matsui WH, Wang Q, Dhodapkar MV, et al. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. ICI Insight 2018; 3: e120505.
73) Yan Z, Cao J, Cheng H, Qiao J, Zhang H, Wang Y, Shi M, Lan J, Fei X, Jin L, et al. A combination of humanized anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Hematol 2019; 6: e521-e529.
74) Wang Y, Cao J, Gu W, Shi M, Lan J, Yan Z, Jin L, Xia J, Ma S, Liu Y, et al. Long-term follow-up of combination of B-cell maturation antigen and CD19 chimeric antigen receptor T cells in multiple myeloma. J Clin Oncol 2022; 40: 2246-2256.
75) Du J, Fu W, Jiang H, Dong B, Gao L, Liu L, Ge J, He A, Li L, Lu J, et al. Updated results of a phase I, open-label study of BCMA/CD19 daul-targeting Fastcar-T GC012F for patients with relapsed/refractory multiple myeloma (RRMM). HemaSphere 2023; 7(S3): e84060bf.
76) Du J, Qiang W, Lu J, Jia Y, He H, Liu J, Guo P, Yang Y, Feng Z, Jin L, et al. Updated results of a phase I open-label single-arm study of dual targeting BCMA and CD19 Fastcar-T cells (GDC012F) as first-line therapy for transplant-eligible newly diagnosed high-risk multiple myeloma. Blood 2023; 142 (suppl. 1): 1022.
77) Shi M, Wang J, Huang H, Liu D, Cheng H, Wang X, Chen W, Yan Z, Sang W, Qi K, Li D, et al. Bispecific CAR T cell therapy targeting BCMA and CD19 in relapsed/refractory multiple myeloma: a phase I/II trial. Nat Commun 2024; 15: 3371.
78) Garfall AL, Cohen AD, Susanibar-Adaniya S, Hwang WT, Vogl DT, Waxman AJ, Lacey SF, Gonzalez VE, Fraietta JA, Gupta M, et al. Anti-BCMA/CD19 CAR T cells with early immunomodulatory maintenance for multiple myeloma responding to initial or later-line therapy. Blood Cancer Discov 2023; 4: 118-133.
79) Li C, Xu J, Luo W, Liao D, Xie W, Wei Q, Zhang Y, Wang X, Wu Z, Kang Y, et al. Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Leukemia 2024; 38: 149-159.
80) Korst C, O’Neill C, Bruins W, Cosovic M, Twickler I, Verkley C, LeCierre D, Themeli M, Chion-Sotinel I, et al. Preclinical activity of allogeneic SLAMF7-specific CAR T-cells (UCARTCS1) in multiple myeloma. J Immunother Cancer 2024; 12: e008769.
81) Gagelmann N, Garderet L, Iacobelli S, Koster L, Carotti A, Schonland S, Galeni P, Daskalakis M, Roeloffzen W, Hunter H, et al. Salvage transplant versus CAR-T cell therapy for relapsed multiple myeloma. Blood 2023; 142 (suppl.1): 3592.
82) Shi X, Yan L, Shang J, Kang L, Yan Z, Jin S, Zhu M, Chang H, Gong F, Zhou J, et al. Anti-CD19 and anti-BCMA CAR T cell therapy followed by lenalidomide maintenance after autologous stem-cell transplantation for high-risk newly diagnosed multiple myeloma. Am J Hematol

Similar Articles

You may also start an advanced similarity search for this article.