Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
28
07
2022
accepted:
11
07
2023
medline:
18
9
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
ppublish
Résumé
Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929 .
Identifiants
pubmed: 37592106
doi: 10.1038/s41591-023-02496-0
pii: 10.1038/s41591-023-02496-0
pmc: PMC10504071
doi:
Substances chimiques
idecabtagene vicleucel
8PX1X7UG4D
Receptors, Chimeric Antigen
0
B-Cell Maturation Antigen
0
Banques de données
ClinicalTrials.gov
['NCT02658929']
Types de publication
Multicenter Study
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2286-2294Informations de copyright
© 2023. The Author(s).
Références
Jagannath, S. et al. Treatment journeys of patients with newly diagnosed multiple myeloma (NDMM): results from the Connect MM Registry. Clin. Lymphoma Myeloma Leuk. 20, 272–276 (2020).
doi: 10.1016/j.clml.2019.10.002
pubmed: 32144027
Kumar, S. K. et al. Multiple myeloma. Nat. Rev. Dis. Primers 3, 17046 (2017).
doi: 10.1038/nrdp.2017.46
pubmed: 28726797
Rajkumar, S. V. & Kumar, S. Multiple myeloma: diagnosis and treatment. Mayo Clin. Proc. 91, 101–119 (2016).
doi: 10.1016/j.mayocp.2015.11.007
pubmed: 26763514
Nijhof, I. S., van de Donk, N., Zweegman, S. & Lokhorst, H. M. Current and new therapeutic strategies for relapsed and refractory multiple myeloma: an update. Drugs 78, 19–37 (2018).
doi: 10.1007/s40265-017-0841-y
pubmed: 29188449
Jagannath, S. et al. KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma. Blood Cancer J. 11, 116 (2021).
doi: 10.1038/s41408-021-00507-2
pubmed: 34145225
pmcid: 8213772
Davies, F. et al. A systematic literature review to assess efficacy of treatments in triple-class exposed relapsed and refractory multiple myeloma patients. Poster EP1033. Proceedings of European Hematology Association (EHA) Virtual Congress (EHA Library, 2020).
Gandhi, U. H. et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia 33, 2266–2275 (2019).
doi: 10.1038/s41375-019-0435-7
pubmed: 30858549
pmcid: 6820050
Holstein, S. A. & Lunning, M. A. CAR T-cell therapy in hematologic malignancies: a voyage in progress. Clin. Pharmacol. Ther. 107, 112–122 (2020).
doi: 10.1002/cpt.1674
pubmed: 31622496
Mikkilineni, L. & Kochenderfer, J. N. CAR T cell therapies for patients with multiple myeloma. Nat. Rev. Clin. Oncol. 18, 71–84 (2021).
doi: 10.1038/s41571-020-0427-6
pubmed: 32978608
Brudno, J. N. & Kochenderfer, J. N. Chimeric antigen receptor T-cell therapies for lymphoma. Nat. Rev. Clin. Oncol. 15, 31–46 (2018).
doi: 10.1038/nrclinonc.2017.128
pubmed: 28857075
Fraietta, J. A. et al. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat. Med. 24, 563–571 (2018).
doi: 10.1038/s41591-018-0010-1
pubmed: 29713085
pmcid: 6117613
Finney, O. C. et al. CD19 CAR T cell product and disease attributes predict leukemia remission durability. J. Clin. Invest. 129, 2123–2132 (2019).
doi: 10.1172/JCI125423
pubmed: 30860496
pmcid: 6486329
Cho, S. F., Anderson, K. C. & Tai, Y. T. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front. Immunol. 9, 1821 (2018).
doi: 10.3389/fimmu.2018.01821
pubmed: 30147690
pmcid: 6095983
Tai, Y. T. et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood 127, 3225–3236 (2016).
doi: 10.1182/blood-2016-01-691162
pubmed: 27127303
pmcid: 4920023
Sanchez, E. et al. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br. J. Haematol. 158, 727–738 (2012).
doi: 10.1111/j.1365-2141.2012.09241.x
pubmed: 22804669
Carpenter, R. O. et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin. Cancer Res. 19, 2048–2060 (2013).
doi: 10.1158/1078-0432.CCR-12-2422
pubmed: 23344265
pmcid: 3630268
Friedman, K. M. et al. Effective targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-B-cell maturation antigen chimeric antigen receptor T cells. Hum. Gene Ther. 29, 585–601 (2018).
doi: 10.1089/hum.2018.001
pubmed: 29641319
pmcid: 5930946
Kawalekar, O. U. et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity 44, 380–390 (2016).
doi: 10.1016/j.immuni.2016.01.021
pubmed: 26885860
Raje, N. et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N. Engl. J. Med. 380, 1726–1737 (2019).
doi: 10.1056/NEJMoa1817226
pubmed: 31042825
pmcid: 8202968
Martin, T. et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin. Oncol. 41, 1265–1274 (2023).
doi: 10.1200/JCO.22.00842
pubmed: 35658469
Munshi, N. C. et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384, 705–716 (2021).
doi: 10.1056/NEJMoa2024850
pubmed: 33626253
Samur, M. K. et al. Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat. Commun. 12, 868 (2021).
doi: 10.1038/s41467-021-21177-5
pubmed: 33558511
pmcid: 7870932
Reyes, K. R., Liu, Y. C., Huang, C. Y. et al. Salvage therapies and clinical outcomes after relapse following BCMA CAR-T in patients with relapsed/refractory multiple myeloma. Proc. 2022 Intern. Myeloma Soc. Annual Meeting and Exposition (2022).
Rodriguez-Otero, P., San-Miguel, J. F., Anderson, L. D. et al. Myeloma/amyloidosis: therapy, excluding transplantation. Proc. 2021 American Soc. Hemat. Ann. Meeting and Exposition (2021).
Abramson, J. S. et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 396, 839–852 (2020).
doi: 10.1016/S0140-6736(20)31366-0
pubmed: 32888407
Neelapu, S. S. et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N. Engl. J. Med. 377, 2531–2544 (2017).
doi: 10.1056/NEJMoa1707447
pubmed: 29226797
pmcid: 5882485
Kochenderfer, J. N. et al. Lymphoma remissions caused by anti-CD19 chimeric antigen receptor T cells are associated with high serum interleukin-15 levels. J. Clin. Oncol. 35, 1803–1813 (2017).
doi: 10.1200/JCO.2016.71.3024
pubmed: 28291388
pmcid: 5455597
Lamure, S. et al. Clinical and product features associated with outcome of DLBCL patients to CD19-targeted CAR T-cell therapy. Cancers (Basel) 13, 4279 (2021).
doi: 10.3390/cancers13174279
pubmed: 34503088
Locke, F. L. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 20, 31–42 (2019).
doi: 10.1016/S1470-2045(18)30864-7
pubmed: 30518502
Lee, D. W. et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124, 188–195 (2014).
doi: 10.1182/blood-2014-05-552729
pubmed: 24876563
pmcid: 4093680
Rajkumar, S. V. et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood 117, 4691–4695 (2011).
doi: 10.1182/blood-2010-10-299487
pubmed: 21292775
pmcid: 3710442
US Food and Drug Administration. Clinical trial endpoints for the approval of cancer drugs and biologics: guidance for industry. https://www.fda.gov/media/71195/download (2018).