Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60. https://doi.org/10.1056/NEJMra1011442.

Article  CAS  PubMed  Google Scholar 

Munshi NC, Anderson LD Jr, Shah N, Madduri D, Berdeja J, Lonial S, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–16. https://doi.org/10.1056/NEJMoa2024850.

Article  CAS  PubMed  Google Scholar 

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(10297):314–24. https://doi.org/10.1016/s0140-6736(21)00933-8.

Article  CAS  PubMed  Google Scholar 

Novak AJ, Darce JR, Arendt BK, Harder B, Henderson K, Kindsvogel W, et al. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689–94. https://doi.org/10.1182/blood-2003-06-2043.

Article  CAS  PubMed  Google Scholar 

Sanchez E, Li M, Kitto A, Li J, Wang CS, Kirk DT, et al. Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival. Br J Haematol. 2012;158(6):727–38. https://doi.org/10.1111/j.1365-2141.2012.09241.x.

Article  CAS  PubMed  Google Scholar 

Rennert P, Schneider P, Cachero TG, Thompson J, Trabach L, Hertig S, et al. A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med. 2000;192(11):1677–84. https://doi.org/10.1084/jem.192.11.1677.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hengeveld PJ, Kersten MJ. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy? Blood Cancer J. 2015;5(2): e282. https://doi.org/10.1038/bcj.2015.3.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seckinger A, Delgado JA, Moser S, Moreno L, Neuber B, Grab A, et al. Target expression, generation, preclinical activity, and pharmacokinetics of the BCMA-T cell bispecific antibody EM801 for multiple myeloma treatment. Cancer Cell. 2017;31(3):396–410. https://doi.org/10.1016/j.ccell.2017.02.002.

Article  CAS  PubMed  Google Scholar 

Hansen DK, Sidana S, Peres LC, Colin Leitzinger C, Shune L, Shrewsbury A, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. 2023;41(11):2087–97. https://doi.org/10.1200/JCO.22.01365.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin Y, Raje NS, Berdeja JG, Siegel DS, Jagannath S, Madduri D, 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(9):2286–94. https://doi.org/10.1038/s41591-023-02496-0.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morrison C. Nanobody approval gives domain antibodies a boost. Nat Rev Drug Discov. 2019;18(7):485–7. https://doi.org/10.1038/d41573-019-00104-w.

Article  CAS  PubMed  Google Scholar 

Martin T, Usmani SZ, Berdeja JG, Agha M, Cohen AD, Hari P, 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. 2023;41(6):1265–74. https://doi.org/10.1200/JCO.22.00842.

Article  CAS  PubMed  Google Scholar 

Schultz LM, Baggott C, Prabhu S, Pacenta HL, Phillips CL, Rossoff J, et al. Disease burden affects outcomes in pediatric and young adult B-cell lymphoblastic leukemia after commercial tisagenlecleucel: a pediatric real-world chimeric antigen receptor consortium report. J Clin Oncol. 2022;40(9):945–55. https://doi.org/10.1200/JCO.20.03585.

Article  CAS  PubMed  Google Scholar 

Da Via MC, Dietrich O, Truger M, Arampatzi P, Duell J, Heidemeier A, et al. Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma. Nat Med. 2021;27(4):616–9. https://doi.org/10.1038/s41591-021-01245-5.

Article  CAS  PubMed  Google Scholar 

Samur MK, Fulciniti M, Aktas Samur A, Bazarbachi AH, Tai YT, Prabhala R, 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(1):868. https://doi.org/10.1038/s41467-021-21177-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Investig. 2019;129(6):2210–21. https://doi.org/10.1172/JCI126397.

Article  PubMed  PubMed Central  Google Scholar 

Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, et al. γ-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat Commun. 2015;6:7333. https://doi.org/10.1038/ncomms8333.

Article  CAS  PubMed  Google Scholar 

Fischer L, Grieb N, Born P, Weiss R, Seiffert S, Boldt A, et al. Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma. Leukemia. 2024. https://doi.org/10.1038/s41375-023-02129-y.

Article  PubMed  PubMed Central  Google Scholar 

Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439–48. https://doi.org/10.1056/NEJMoa1709866.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380(1):45–56. https://doi.org/10.1056/NEJMoa1804980.

Article  CAS  PubMed  Google Scholar 

Fraietta JA, Lacey SF, Orlando EJ, Pruteanu-Malinici I, Gohil M, Lundh S, et al. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med. 2018;24(5):563–71. https://doi.org/10.1038/s41591-018-0010-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF, et al. A human memory T cell subset with stem cell-like properties. Nat Med. 2011;17(10):1290–7. https://doi.org/10.1038/nm.2446.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014;123(24):3750–9. https://doi.org/10.1182/blood-2014-01-552174.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henning AN, Roychoudhuri R, Restifo NP. Epigenetic control of CD8(+) T cell differentiation. Nat Rev Immunol. 2018;18(5):340–56. https://doi.org/10.1038/nri.2017.146.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yoshikawa T, Wu Z, Inoue S, Kasuya H, Matsushita H, Takahashi Y, et al. Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy. Blood. 2022;139(14):2156–72. https://doi.org/10.1182/blood.2021012714.

Article  CAS  PubMed  Google Scholar 

Jung IY, Narayan V, McDonald S, Rech AJ, Bartoszek R, Hong G, et al. BLIMP1 and NR4A3 transcription factors reciprocally regulate antitumor CAR T cell stemness and exhaustion. Sci Transl Med. 2022;14(670):eabn7336. https://doi.org/10.1126/scitranslmed.abn7336.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF, 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(19):9543–51. https://doi.org/10.1073/pnas.1819745116.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wagner DL, Fritsche E, Pulsipher MA, Ahmed N, Hamieh M, Hegde M, et al. Immunogenicity of CAR T cells in cancer therapy. Nat Rev Clin Oncol. 2021;18(6):379–93. https://doi.org/10.1038/s41571-021-00476-2.

Article  PubMed  PubMed Central  Google Scholar 

Dahlhoff J, Manz H, Steinfatt T, Delgado-Tascon J, Seebacher E, Schneider T, et al. Transient regulatory T-cell targeting triggers immune control of multiple myeloma and prevents disease progression. Leukemia. 2022;36(3):790–800. https://doi.org/10.1038/s41375-021-01422-y.

Article  CAS  PubMed  Google Scholar 

Görgün GT, Whitehill G, Anderson JL, Hideshima T, Maguire C, Laubach J, et al. Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood. 2013;121(15):2975–87. https://doi.org/10.1182/blood-2012-08-448548.

Article  CAS  PubMed  PubMed Central