nach oben

memo - Magazine of European Medical Oncology

Erschienen in:

17.08.2022 | short review

CAR T cells in multiple myeloma: Where we stand and where we might be going

verfasst von: PD Dr. Niklas Zojer, Dr. Martin Schreder, Univ.-Prof. Dr. Heinz Ludwig

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 3/2022

Einloggen, um Zugang zu erhalten

Summary

In this review we highlight the current developments in Chimeric antigen receptor (CAR) T cell therapy for myeloma. Two advanced products (idecabtagene vicleucel and ciltacabtagene autoleucel) targeting B‑cell maturation antigen have already been approved by the US Food and Drug Administration (FDA). In heavily pretreated myeloma patients, response rates between 82 and 98% and a median progression-free survival between 12 and > 24 months have been achieved. Currently these two products are being investigated in earlier lines of therapy. Beside BCMA, other targets have been selected for CAR T cell therapy in myeloma, with advanced constructs targeting two antigens. We highlight current strategies to improve CAR T cell effectiveness and safety and give a personal outlook where cellular immunotherapy in myeloma might be heading.

Vorheriger Artikel Real time experience applying CAR T-cells for B-cell lymphoma—What we have learned so far: Acute toxicity management

Nächster Artikel Applicability of ESMO-MCBS and ESCAT for molecular tumor boards

Teoh PJ, Chng WJ. CAR T‑cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 2021;11(4):84.CrossRef

Munshi NC, Anderson LD, Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–16.CrossRef

Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: phase 1b/2study of ciltacabtagene autoleucel, a B-cell maturation antigen—directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Abstract. 63rd ASH Annual Meeting & Exposition. Vol. 549. 2021.

Mateos MV, Weisel K, Martin T, et al. Ciltacabtagene autoleucel for triple-class exposed multiple myeloma: adjusted comparisons of CARTITUDE-1 patient outcomes versus therapies from real-world clinical practice from the LocoMMotion prospective study. Abstract. 63rd ASH Annual Meeting & Exposition. Vol. 550. 2021.

Van de Donk NW, Themeli M, Usmani SZ. Determinants of response and mechanisms of resistance of CAR T‑cell therapy in multiple myeloma. Blood Cancer Discov. 2021;2(4):302–18.CrossRef

Manier S, Ingegnere T, Escure G, et al. Current state and next-generation CAR‑T cells in multiple myeloma. Blood Rev. 2022; https://doi.org/10.1016/j.blre.2022.100929.CrossRefPubMed

Atamaniuk J, Gleiss A, Porpaczy E, et al. Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma. Eur J Clin Invest. 2012;42(9):953–60.CrossRef

Mailankody S, Diamonte C, Fitzgerald L, et al. Phase I first-in-class trial of MCARH109, a G protein coupled receptor class C group 5 member D (GPRC5D) targeted CAR T cell therapy in patients with relapsed or refractory multiple myeloma. Abstract. 63rd ASH Annual Meeting & Exposition. Vol. 827. 2021.

Zah E, Nam E, Bhuvan V, et al. Systematically optimized BCMA/CS1 bispecific CAR‑T cells robustly control heterogeneous multiple myeloma. Nat Commun. 2020;11(1):2283.CrossRef

10.

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.CrossRef

11.

Van de Donk NW, Usmani SZ, Yong K. CAR T‑cell therapy for multiple myeloma: state of the art and prospects. Lancet Haematol. 2021;8(6):e446–e61. https://doi.org/10.1016/S2352-3026(21)00057-0.CrossRefPubMed

12.

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. Lancet. 2021;398(10297):314–24.CrossRef

13.

Mailankody S, Jakubowiak AJ, Htut M, 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.CrossRef

14.

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. Abstract. 63rd ASH Annual Meeting & Exposition. Vol. 548. 2021.

15.

Mailankody S, Liedtke M, Sidana S, et al. Universal updated phase 1 data validates the feasibility of allogeneic anti-BCMA ALLO-715 therapy for relapsed/refractory multiple myeloma. Abstract. 63rd ASH Annual Meeting & Exposition. Vol. 651. 2021.

16.

Pont MJ, Hill T, O’Cole G, et al. γ‑Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. Blood. 2019;134(19):1585–97.CrossRef

17.

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):1726–37.CrossRef

18.

Mestermann K, Giavridis T, Weber J, et al. The tyrosine kinase inhibitor dasatinib acts as a pharmacologic on/off switch for CAR T cells. Sci Transl Med. 2019;11(499):eaau5907.CrossRef

19.

Van Oekelen O, Aleman A, Upadhyaya B, et al. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR‑T cell therapy. Nat Med. 2021;27(12):2099–103.CrossRef

20.

Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020;17(3):147–67.CrossRef

21.

Fedorov VD, Themeli M, Sadelain M. PD-1- and CTLA-4-based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses. Sci Transl Med. 2013;5(215):215ra172.CrossRef

22.

Xie G, Dong H, Liang Y, et al. CAR-NK cells: a promising cellular immunotherapy for cancer. eBioMedicine. 2020;59:102975. https://doi.org/10.1016/j.ebiom.2020.102975.CrossRefPubMedPubMedCentral

23.

Moscarelli J, Zahavi D, Maynard R, Weiner LM. The next generation of cellular immunotherapy: CAR-NK cells. Transplant Cell Ther. 2022; https://doi.org/10.1016/j.jtct.2022.06.025.CrossRefPubMed

24.

Carbone E, Neri P, Mesuraca M, et al. HLA class I, NKG2D, and natural cytotoxicity receptors regulate multiple myeloma cell recognition by natural killer cells. Blood. 2005;105(1):251–8.CrossRef

25.

Chu J, Deng Y, Benson DM, et al. CS1-specific chimeric antigen receptor (CAR)-engineered natural killer cells enhance in vitro and in vivo antitumor activity against human multiple myeloma. Leukemia. 2014;28(4):917–27.CrossRef

26.

Jiang H, Zhang W, Shang P, et al. Transfection of chimeric anti-CD138 gene enhances natural killer cell activation and killing of multiple myeloma cells. Mol Oncol. 2014;8(2):297–310.CrossRef

27.

Poels R, Drent E, Lameris R, et al. Preclinical evaluation of invariant natural killer T cells modified with CD38 or BCMA chimeric antigen receptors for multiple myeloma. Int J Mol Sci. 2021;22(3):1096.CrossRef

28.

Leivas A, Valeri A, Codoba L, et al. NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma. Blood Cancer J. 2021;11(8):146.CrossRef

Titel: CAR T cells in multiple myeloma: Where we stand and where we might be going
verfasst von: PD Dr. Niklas Zojer
Dr. Martin Schreder
Univ.-Prof. Dr. Heinz Ludwig
Publikationsdatum: 17.08.2022
Verlag: Springer Vienna
Erschienen in: memo - Magazine of European Medical Oncology / Ausgabe 3/2022
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI: https://doi.org/10.1007/s12254-022-00825-6

Molecular profiling in colorectal cancer

short review

Neoadjuvant treatment of pancreatic ductal adenocarcinoma

short review

Real time experience applying CAR T-cells for B-cell lymphoma—What we have learned so far: Acute toxicity management

short review

Multiple myeloma with central nervous system relapse: a case report

case report

Neoadjuvant treatment in gastric cancer

short review

Systemic inflammatory response index is a prognostic biomarker in unresectable pancreatic adenocarcinoma and identifies patients for more intensive treatment

original report

Springer Medizin Österreich

CAR T cells in multiple myeloma: Where we stand and where we might be going

Summary

Weitere Artikel der Ausgabe 3/2022

Molecular profiling in colorectal cancer

Neoadjuvant treatment of pancreatic ductal adenocarcinoma

Real time experience applying CAR T-cells for B-cell lymphoma—What we have learned so far: Acute toxicity management

Multiple myeloma with central nervous system relapse: a case report

Neoadjuvant treatment in gastric cancer

Systemic inflammatory response index is a prognostic biomarker in unresectable pancreatic adenocarcinoma and identifies patients for more intensive treatment

Springer Medizin Österreich

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Molecular profiling in colorectal cancer

Neoadjuvant treatment of pancreatic ductal adenocarcinoma

Real time experience applying CAR T-cells for B-cell lymphoma—What we have learned so far: Acute toxicity management

Multiple myeloma with central nervous system relapse: a case report

Neoadjuvant treatment in gastric cancer

Systemic inflammatory response index is a prognostic biomarker in unresectable pancreatic adenocarcinoma and identifies patients for more intensive treatment