CAR-T cell therapy in Multiple Myeloma: current status and future challenges

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

Article  PubMed  Google Scholar 

Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21–33.

Article  PubMed  Google Scholar 

Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364:1046–60.

Article  CAS  PubMed  Google Scholar 

Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015;33:2863–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Avet-Loiseau H. Ultra high-risk myeloma. Hematol Am Soc Hematol Educ Program. 2010;2010:489–93.

Article  Google Scholar 

Weinhold N, Ashby C, Rasche L, Chavan SS, Stein C, Stephens OW, et al. Clonal selection and double-hit events involving tumor suppressor genes underlie relapse in myeloma. Blood 2016;128:1735–44.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weinhold N, Heuck CJ, Rosenthal A, Thanendrarajan S, Stein CK, Van Rhee F, et al. Clinical value of molecular subtyping multiple myeloma using gene expression profiling. Leukemia 2016;30:423–30.

Article  CAS  PubMed  Google Scholar 

Gandhi UH, Cornell RF, Lakshman A, Gahvari ZJ, McGehee E, Jagosky MH, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 2019;33:2266–75.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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

Article  CAS  PubMed  PubMed Central  Google Scholar 

Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–60.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 2016;128:1688–700.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, 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;36:2267–80.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl J Med. 2019;380:1726–37.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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;384:705–16.

Article  CAS  PubMed  Google Scholar 

Anderson JLD, Munshi NC, Shah N, Jagannath S, Berdeja JG, Lonial S, et al. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T cell therapy, in relapsed and refractory multiple myeloma: updated KarMMa results. J Clin Oncol. 2021;39:8016.

Article  Google Scholar 

Manier S, Kansagra AJ, Anderson JLD, Berdeja JG, Jagannath S, Lin Y, et al. Characteristics of neurotoxicity associated with idecabtagene vicleucel (ide-cel, bb2121) in patients with relapsed and refractory multiple myeloma (RRMM) in the pivotal phase II KarMMa study. J Clin Oncol. 2021;39:8036.

Article  Google Scholar 

Usmani S, Patel K, Hari P, Berdeja J, Alsina M, Vij 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 2022;140:875–7.

Article  Google Scholar 

Dhodapkar MV, Alsina M, Berdeja JG, Patel KK, Richard S, Vij R, et al. Efficacy and Safety of Idecabtagene Vicleucel (ide-cel) in Patients with Clinical High-Risk Newly Diagnosed Multiple Myeloma (NDMM) with an Inadequate Response to Frontline Autologous Stem Cell Transplantation (ASCT): KarMMa-2 Cohort 2c Extended Follow-up. Blood 2023;142:2101.

Article  Google Scholar 

Rodríguez Otero P, Ailawadhi S, Arnulf B, Patel KK, Cavo M, Nooka AK, et al. Idecabtagene Vicleucel (ide-cel) Versus Standard (std) Regimens in Patients (pts) with Triple-Class-Exposed (TCE) Relapsed and Refractory Multiple Myeloma (RRMM): Updated Analysis from KarMMa-3. Blood 2023;142:1028.

Article  Google Scholar 

Ailawadhi S, Arnulf B, Patel KK, Cavo M, Nooka AK, Manier S, et al. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood. 2024.

Zhao WH, Liu J, Wang BY, Chen YX, Cao XM, Yang Y, 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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu J, Chen L-J, Yang S-S, Sun Y, Wu W, Liu Y-F, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci USA. 2019;116:9543–51.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mi J-Q, Zhao W-H, Chen L-J, Fu W-J, Wang B-Y, Xu J, et al. Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment of LCAR-B38M CAR-T: At least 5-year follow-up in LEGEND-2. J Clin Oncol. 2023;41:8010.

Article  Google Scholar 

03.08.2024 hwfgmda.

Berdeja JG, Madduri D, Usmani SZ, Jakubowiak A, Agha M, Cohen AD, 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;398:314–24.

Article  CAS  PubMed  Google Scholar 

Martin T, Usmani SZ, Berdeja JG, Jakubowiak A, Agha M, Cohen AD, 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. Blood 2021;138:549.

Article  Google Scholar 

Jakubowiak A, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, et al. Efficacy and Safety of Ciltacabtagene Autoleucel in Patients With Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 Subgroup Analysis. Blood 2021;138:3938.

Article  Google Scholar 

Lin Y, Martin TG, Usmani SZ, Berdeja JG, Jakubowiak AJ, Agha ME, et al. CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2023;41:8009.

Article  Google Scholar 

Hillengass J, Cohen AD, Agha ME, Delforge M, Kerre T, Roeloffzen W, et al. The Phase 2 CARTITUDE-2 Trial: Updated Efficacy and 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;142:1021.

Article  Google Scholar 

Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Paiva B, van de Donk N, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood 2023;141:219–30.

Article  CAS  PubMed  Google Scholar 

San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. N. Engl J Med. 2023;389:335–47.

Article  CAS  PubMed  Google Scholar 

Mateos M-VS-MJ, San-Miguel J, Dhakal B, Touzeau C, Leleu X, van de Donk N et al. Overall survival (OS) with ciltacabtagene autoleucel (cilta-cel) versus standard of care (SoC) in lenalidomide (len)-refractory multiple myeloma (MM): phase 3 CARTITUDE-4 study update. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil Abstract OA – 65.

Dytfeld D, Dhakal B, Agha M, Manier S, Delforge M, Kuppens S, et al. Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed By Ciltacabtagene Autoleucel Versus Vrd Followed By Lenalidomide and Dexamethasone (Rd) Maintenance in Patients with Newly Diagnosed Multiple Myeloma Not Intended for Transplant: A Randomized, Phase 3 Study (CARTITUDE-5). Blood 2021;138:1835.

Article  Google Scholar 

van de Donk N, Usmani SZ, Yong K. CAR T-cell therapy for multiple myeloma: state of the art and prospects. Lancet Haematol. 2021;8:e446–e61.

Article  PubMed  Google Scholar 

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;11:283.

留言 (0)

沒有登入
gif