Single-cell multiomic dissection of response and resistance to chimeric antigen receptor T cells against BCMA in relapsed multiple myeloma

Merz, M. et al. Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple Myeloma Patients with Prior Exposure to PI, Imid and Anti-CD-38 from a German Registry. Cancers 13, 5996 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Munshi, N. C. et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384, 705–716 (2021).

Article  CAS  PubMed  Google Scholar 

Berdeja, J. G. 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 398, 314–324 (2021).

Article  CAS  PubMed  Google Scholar 

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 (2022).

Da Vià, M. C. et al. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat. Med. 27, 616–619 (2021).

Article  PubMed  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gagelmann, N. et al. Access to and affordability of CAR T-cell therapy in multiple myeloma: an EBMT position paper. Lancet Haematol. 9, e786–e795 (2022).

Article  CAS  PubMed  Google Scholar 

Gazeau, N. et al. Effective anti-BCMA retreatment in multiple myeloma. Blood Adv. 5, 3016–3020 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Deng, H. et al. Efficacy of humanized anti-BCMA CAR T cell therapy in relapsed/refractory multiple myeloma patients with and without extramedullary disease. Front. Immunol. 12, 720571 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Haradhvala, N. J. et al. Distinct cellular dynamics associated with response to CAR-T therapy for refractory B cell lymphoma. Nat. Med. 28, 1848–1859 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sheih, A. et al. Clonal kinetics and single-cell transcriptional profiling of CAR-T cells in patients undergoing CD19 CAR-T immunotherapy. Nat. Commun. 11, 219 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bai, Z. et al. Single-cell antigen-specific landscape of CAR T infusion product identifies determinants of CD19-positive relapse in patients with ALL. Sci. Adv. 8, eabj2820 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boiarsky, R. et al. Single cell characterization of myeloma and its precursor conditions reveals transcriptional signatures of early tumorigenesis. Nat. Commun. 13, 7040 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen, Y. C. et al. Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing. Nat. Med. 27, 491–503 (2021).

Dutta, A. K. et al. Single-cell profiling of tumour evolution in multiple myeloma—opportunities for precision medicine. Nat. Rev. Clin. Oncol. 19, 223–236 (2022).

Ledergor, G. et al. Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma. Nat. Med. 24, 1867–1876 (2018).

Article  CAS  PubMed  Google Scholar 

Merz, M. et al. Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma. Nat. Commun. 13, 807 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Phipson, B. et al. propeller: testing for differences in cell type proportions in single cell data. Bioinformatics 38, 4720–4726 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

van der Leun, A. M., Thommen, D. S. & Schumacher, T. N. CD8+ T cell states in human cancer: insights from single-cell analysis. Nat. Rev. Cancer 20, 218–232 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Cohen, A. D. et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J. Clin. Invest. 129, 2210–2221 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Nakamura, K., Smyth, M. J. & Martinet, L. Cancer immunoediting and immune dysregulation in multiple myeloma. Blood 136, 2731–2740 (2020).

Article  CAS  PubMed  Google Scholar 

Merz, M. et al. Spatiotemporal assessment of immunogenomic heterogeneity in multiple myeloma. Blood Adv. 7, 718–733 (2022).

Zavidij, O. et al. Single-cell RNA sequencing reveals compromised immune microenvironment in precursor stages of multiple myeloma. Nat. Cancer 1, 493–506 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clements, A. N. & Warfel, N. A. Targeting PIM kinases to improve the efficacy of immunotherapy. Cells 11, 3700 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Keane, N. A., Reidy, M., Natoni, A., Raab, M. S. & O’Dwyer, M. Targeting the Pim kinases in multiple myeloma. Blood Cancer J. 5, e325 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chatterjee, S. et al. Targeting PIM kinase with PD1 inhibition improves immunotherapeutic antitumor T-cell response. Clin. Cancer Res. 25, 1036–1049 (2019).

Article  CAS  PubMed  Google Scholar 

Moesta, A. K., Li, X.-Y. & Smyth, M. J. Targeting CD39 in cancer. Nat. Rev. Immunol. 20, 739–755 (2020).

Article  CAS  PubMed  Google Scholar 

Vucinic, V. et al. S287: factors influencing autologous lymphocyte collections for chimeric antigen receptor (CAR) T-cells—the role of T-cell senescence. HemaSphere 6, 188 (2022).

Article  Google Scholar 

Chen, P.-H. et al. Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy. JCI Insight 5, e134612 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Dhodapkar, K. M. et al. Changes in bone marrow tumor and immune cells correlate with durability of remissions following BCMA CAR T therapy in myeloma. Blood Cancer Discov. 3, 490–501 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mathewson, N. D. et al. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell 184, 1281–1298 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Melenhorst, J. J. et al. Decade-long leukaemia remissions with persistence of CD4+ CAR T cells. Nature 602, 503–509 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang, B. et al. Chimeric antigen receptor T cell therapy in the relapsed or refractory multiple myeloma with extramedullary disease—a single institution observation in China. Blood 136, 6 (2020).

Article  Google Scholar 

García-Guerrero, E. et al. All-trans retinoic acid works synergistically with the γ-secretase inhibitor crenigacestat to augment BCMA on multiple myeloma and the efficacy of BCMA-CAR T cells. Haematologica 108, 568–580 (2023).

Article  PubMed  Google Scholar 

Merz, M. et al. Cytogenetic subclone formation and evolution in progressive smoldering multiple myeloma. Leukemia 34, 1192–1196 (2020).

Article  PubMed  Google Scholar 

Merz, M. et al. Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma. Blood Adv. 2, 1–9 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Kumar, S. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 17, e328–e346 (2016).

Article  PubMed  Google Scholar 

Campbell, T. et al. Uses of anti-BCMA chimeric antigen receptors. Worldwide patent WO2021091978A1 (2021).

Schecter, J. M. & Fan, X. BCMA-targeted CAR-T cell therapy for multiple myeloma. Worldwide patent WO2022116086A1 (2022).

Germain, P.-L., Lun, A., Meixide, C. G., Macnair, W. & Robinson, M. D. Doublet identification in single-cell sequencing data using scDblFinder. F1000Res. 10, 979 (2022).

Aran, D. et al. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat. Immunol. 20, 163–172 (2019).

Article  CAS  PubMed  PubMed Central 

Comments (0)

No login
gif