The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma

References

• Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309–322. doi: 10.1016/j.annonc.2020.11.014
   PubMed Web of Science ®Google Scholar
• Callander NS, Baljevic M, Adekola K, et al. NCCN guidelines(R) insights: multiple myeloma, version 3.2022. J Natl Compr Canc Netw. 2022 Jan;20(1):8–19.
   PubMed Web of Science ®Google Scholar
• Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. Leukemia. [2019 Sep];33(9):2266–2275. doi: 10.1038/s41375-019-0435-7
   PubMed Web of Science ®Google Scholar
• Mateos MV, Weisel K, De Stefano V, et al. LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia. 2022 May;36(5):1371–1376.
   PubMed Web of Science ®Google Scholar
• Joseph NS, Kaufman JL, Dhodapkar MV, et al. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol. 2020 Jun 10;38(17):1928–1937. doi: 10.1200/JCO.19.02515
   PubMed Web of Science ®Google Scholar
• Podar K, Jager D. Targeting the immune niche within the bone marrow microenvironment: the rise of immunotherapy in multiple myeloma. Curr Cancer Drug Targets. 2017;17(999):1–1. doi: 10.2174/1568009617666170214103834
   Google Scholar
• Kuwana Y, Asakura Y, Utsunomiya N, et al. Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions. Biochem Biophys Res Commun. 1987 Dec 31;149(3):960–968. doi: 10.1016/0006-291X(87)90502-X
   PubMed Web of Science ®Google Scholar
• Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10024–8. doi: 10.1073/pnas.86.24.10024
   PubMed Web of Science ®Google Scholar
• Sadelain M, Brentjens R, Riviere I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388–398. doi: 10.1158/2159-8290.CD-12-0548
   PubMed Web of Science ®Google Scholar
• Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity. 2013;39(1):49–60. doi: 10.1016/j.immuni.2013.07.002
   PubMed Web of Science ®Google Scholar
• Irving BA, Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-O
   PubMed Web of Science ®Google Scholar
• Romeo C, Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037–46. doi: 10.1016/0092-8674(91)90327-U
   PubMed Web of Science ®Google Scholar
• Letourneur F, Klausner RD. T-cell and basophil activation through the cytoplasmic tail of T-cell-receptor zeta family proteins. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8905–9. doi: 10.1073/pnas.88.20.8905
   PubMed Web of Science ®Google Scholar
• Bird RE, Hardman KD, Jacobson JW, et al. Single-chain antigen-binding proteins. Science. 1988 Oct 21;242(4877):423–6. doi: 10.1126/science.3140379
   PubMed Web of Science ®Google Scholar
• Eshhar Z, Waks T, Gross G, et al. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):720–4. doi: 10.1073/pnas.90.2.720
   PubMed Web of Science ®Google Scholar
• Moritz D, Wels W, Mattern J, et al. Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4318–22. doi: 10.1073/pnas.91.10.4318
   PubMed Web of Science ®Google Scholar
• Hwu P, Shafer GE, Treisman J, et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. J Exp Med. 1993 Jul 1;178(1):361–6. doi: 10.1084/jem.178.1.361
   PubMed Web of Science ®Google Scholar
• Hwu P, Yang JC, Cowherd R, et al. In vivo antitumor activity of T cells redirected with chimeric antibody/T-cell receptor genes. Cancer Res. 1995 Aug 1;55(15):3369–73.
   PubMed Web of Science ®Google Scholar
• Kershaw MH, Westwood JA, Parker LL, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. 2006;12(20 Pt 1):6106–6115. doi: 10.1158/1078-0432.CCR-06-1183
   PubMed Web of Science ®Google Scholar
• Lamers CH, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006 May 1;24(13):e20–2. doi: 10.1200/JCO.2006.05.9964
   PubMedGoogle Scholar
• Park JR, Digiusto DL, Slovak M, et al. Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma. Mol Ther. 2007 Apr;15(4):825–33.
   PubMed Web of Science ®Google Scholar
• Pule MA, Savoldo B, Myers GD, et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008 Nov;14(11):1264–70.
   PubMed Web of Science ®Google Scholar
• Krause A, Guo HF, Latouche JB, et al. Antigen-dependent CD28 signaling selectively enhances survival and proliferation in genetically modified activated human primary T lymphocytes. J Exp Med. 1998 Aug 17;188(4):619–26. doi: 10.1084/jem.188.4.619
   PubMed Web of Science ®Google Scholar
• Maher J, Brentjens RJ, Gunset G, et al. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002 Jan;20(1):70–75.
   PubMed Web of Science ®Google Scholar
• Savoldo B, Ramos CA, Liu E, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011 May;121(5):1822–1826.
   PubMed Web of Science ®Google Scholar
• Hombach A, Wieczarkowiecz A, Marquardt T, et al. Tumor-specific T cell activation by recombinant immunoreceptors: CD3 zeta signaling and CD28 costimulation are simultaneously required for efficient IL-2 secretion and can be integrated into one combined CD28/CD3 zeta signaling receptor molecule. J Immunol. 2001 Dec 1;167(11):6123–6131. doi: 10.4049/jimmunol.167.11.6123
   PubMed Web of Science ®Google Scholar
• Finney HM, Akbar AN, Lawson AD. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR zeta chain. J Immunol. 2004 Jan 1;172(1):104–113. doi: 10.4049/jimmunol.172.1.104
   PubMed Web of Science ®Google Scholar
• Imai C, Mihara K, Andreansky M, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004 Apr;18(4):676–84. doi: 10.1038/sj.leu.2403302
   PubMed Web of Science ®Google Scholar
• Milone MC, Fish JD, Carpenito C, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009 Aug;17(8):1453–64.
   PubMed Web of Science ®Google Scholar
• Brentjens RJ, Latouche JB, Santos E, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med. 2003 Mar;9(3):279–86.
   PubMed Web of Science ®Google Scholar
• Porter DL, Levine BL, Kalos M, et al. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011 Aug 25;365(8):725–733. doi: 10.1056/NEJMoa1103849
   PubMed Web of Science ®Google Scholar
• Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-Cell lymphoblastic leukemia. N Engl J Med. 2018 Feb 1;378(5):439–448. doi: 10.1056/NEJMoa1709866
   PubMed Web of Science ®Google Scholar
• Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-Cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531–2544. doi: 10.1056/NEJMoa1707447
   PubMed Web of Science ®Google Scholar
• Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020 Apr 2;382(14):1331–1342. doi: 10.1056/NEJMoa1914347
   PubMed Web of Science ®Google Scholar
• Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-Cell lymphoma. N Engl J Med. 2019 Jan 3;380(1):45–56. doi: 10.1056/NEJMoa1804980
   PubMed Web of Science ®Google Scholar
• Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839–852. doi: 10.1016/S0140-6736(20)31366-0
   PubMed Web of Science ®Google Scholar
• Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-Cell lymphoma. N Engl J Med. 2022 Feb 17;386(7):640–654. doi: 10.1056/NEJMoa2116133
   PubMed Web of Science ®Google Scholar
• Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022 Jun 18;399(10343):2294–2308. doi: 10.1016/S0140-6736(22)00662-6
   PubMed Web of Science ®Google Scholar
• Garfall AL, Maus MV, Hwang W-T, et al. Chimeric antigen receptor T Cells against CD19 for multiple myeloma. New Engl J Med. 2015;373(11):1040–7. doi: 10.1056/NEJMoa1504542
   PubMed Web of Science ®Google Scholar
• Tai YT, Anderson KC. B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma. Expert Opin Biol Ther. 2019 Nov;19(11):1143–1156. doi: 10.1080/14712598.2019.1641196
   PubMed Web of Science ®Google Scholar
• Ali SA, Shi V, Maric I, et al. T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016;128(13):1688–1700. doi: 10.1182/blood-2016-04-711903
   PubMed Web of Science ®Google Scholar
• Munshi NC, Anderson LD Jr., Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021 Feb 25;384(8):705–716. doi: 10.1056/NEJMoa2024850
   PubMed Web of Science ®Google Scholar
• Lin Y, Raje NS, Berdeja JG, et al. Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial. Nat Med. 2023 Sep;29(9):2286–2294.
   PubMed Web of Science ®Google Scholar
• 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):314–324. doi: 10.1016/S0140-6736(21)00933-8
   PubMed Web of Science ®Google Scholar
• Dotti G, Gottschalk S, Savoldo B, et al. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107–26.
   PubMed Web of Science ®Google Scholar
• Jayaraman J, Mellody MP, Hou AJ, et al. CAR-T design: elements and their synergistic function. EBioMedicine. 2020 Aug;58:102931.
   PubMed Web of Science ®Google Scholar
• Teoh PJ, Chng WJ. CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 2021 Apr 29;11(4):84. doi: 10.1038/s41408-021-00469-5
   PubMed Web of Science ®Google Scholar
• Miliotou AN, Papadopoulou LC. CAR T-cell therapy: a new era in cancer immunotherapy. Curr Pharm Biotechnol. 2018;19(1):5–18. doi: 10.2174/1389201019666180418095526
   PubMed Web of Science ®Google Scholar
• Jin C, Yu D, Hillerdal V, et al. Allogeneic lymphocyte-licensed DCs expand T cells with improved antitumor activity and resistance to oxidative stress and immunosuppressive factors. Mol Ther Methods Clin Dev. 2014;1:14001. doi: 10.1038/mtm.2014.1
   PubMed Web of Science ®Google Scholar
• Jin J, Cheng J, Huang M, et al. Fueling chimeric antigen receptor T cells with cytokines. Am J Cancer Res. 2020;10(12):4038–4055.
   PubMed Web of Science ®Google Scholar
• Janssen Biotech I. CARVYKTI (ciltacabtagene autoleucel). Prescribing Information https://wwwfdagov/media/156560/download
   Google Scholar
• Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–854. doi: 10.1126/science.1076514
   PubMed Web of Science ®Google Scholar
• Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346–57. doi: 10.1200/JCO.2005.00.240
   PubMed Web of Science ®Google Scholar
• Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62–8. doi: 10.1126/science.aaa4967
   PubMed Web of Science ®Google Scholar
• Zhao WH, Liu J, Wang BY, 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 Dec 20;11(1):141. doi: 10.1186/s13045-018-0681-6
   PubMedGoogle Scholar
• Zhao WH, Wang BY, Chen LJ, et al. Four-year follow-up of LCAR-B38M in relapsed or refractory multiple myeloma: a phase 1, single-arm, open-label, multicenter study in China (LEGEND-2). J Hematol Oncol. 2022 Jul 6;15(1):86. doi: 10.1186/s13045-022-01301-8
   PubMed Web of Science ®Google Scholar
• Mi J, Zhao W, Chen L, et al. P874: 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. Hemasphere. 2023;7(S3):1641–42. doi: 10.1097/01.HS9.0000970400.98418.89
   Google Scholar
• Martin T, Usmani SZ, Berdeja JG, 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 Feb 20;41(6):1265–1274. doi: 10.1200/JCO.22.00842
   PubMed Web of Science ®Google Scholar
• Munshi N, Martin T, Usmani SZ, et al. S202: cartitude-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Hemasphere. 2023;7(S3):232–33 abstr 202. doi: 10.1097/01.HS9.0000967720.61024.68
   Google Scholar
• Lin Y, Martin TG, Usmani SZ, 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(16_suppl):abstr 8009. doi: 10.1200/JCO.2023.41.16_suppl.8009
   Web of Science ®Google Scholar
• Jagannath S, Martin T, Usmani S. P-275 CARTITUDE-1 final results: phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2023;23:–275. doi: 10.1016/S2152-2650(23)01893-1
   Google Scholar
• Htut M, Dhakal B, Cohen AD, et al. Ciltacabtagene autoleucel in patients with prior allogeneic stem cell transplant in the CARTITUDE-1 study. Clin Lymphoma Myeloma Leuk. 2023 Aug 22;23(12):882–888. doi: 10.1016/j.clml.2023.08.012
   PubMed Web of Science ®Google Scholar
• Hillengass J, Cohen AC, Agha ME, 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(Supplement 1):1021. doi: 10.1182/blood-2023-178882
   Google Scholar
• Cohen AD, Cohen Y, Suvannasankha A, et al. Efficacy and safety of ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma and prior noncellular anti‐BCMA therapy: CARTITUDE‐2 cohort C. Clin Lymphoma Myeloma Leuk. 2023;167:240.
   Google Scholar
• Cohen AD, Mateos MV, Cohen YC, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023 Jan 19;141(3):219–230. doi: 10.1182/blood.2022015526
   PubMed Web of Science ®Google Scholar
• San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023 Jul 27;389(4):335–347. doi: 10.1056/NEJMoa2303379
   PubMed Web of Science ®Google Scholar
• Manier S, San-Miguel J, Dhakal B. OA-47 additional analysis of CARTITUDE-4: cilta-cel vs standard of care (PVd or DPd) in lenalidomide-refractory patients with multiple myeloma and 1–3 prior lines of therapy. Clin Lymphoma Myeloma Leuk. 2023;23:S29–S30. doi: 10.1016/S2152-2650(23)01614-2
   Web of Science ®Google Scholar
• Fernandez de Larrea C, Harrison S, Martinez-Lopez J. Pharmacokinetic and correlative analysis of ciltacabtagene autoleucel in patients with lenalidomide-refractory multiple myeloma in CARTITUTE-4 trial. Clin Lymphoma Myeloma Leuk. 2023;23:OA–45. doi: 10.1016/S2152-2650(23)01612-9
   Web of Science ®Google Scholar
• Mi JQ, Zhao W, Jing H, et al. Phase II, Open-Label Study of Ciltacabtagene autoleucel, an anti-B-Cell maturation antigen chimeric antigen receptor-T-Cell Therapy, in Chinese patients with relapsed/refractory multiple myeloma (CARTIFAN-1). J Clin Oncol. 2023 Feb 20;41(6):1275–1284. doi: 10.1200/JCO.22.00690
   PubMed Web of Science ®Google Scholar
• Al Hadidi S, Cliff ERS. CARTIFAN-1: concerning fatal adverse events with global use of chimeric antigen receptor-T-cell therapy in multiple myeloma. Eur J Cancer. 2023 Mar;182:1–2. doi: 10.1016/j.ejca.2022.12.018
   PubMed Web of Science ®Google Scholar
• Hansen DK, Patel KK, Peres LC, et al. Safety and efficacy of standard of care (SOC) ciltacabtagene autoleucel (Cilta-cel) for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16_suppl):abstr 8012. doi: 10.1200/JCO.2023.41.16_suppl.8012
   Google Scholar
• Costa LJ, Lin Y, Cornell RF, et al. Comparison of Cilta-cel, an anti-BCMA CAR-T cell therapy, versus conventional treatment in patients with Relapsed/Refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2022 May;22(5):326–335.
   PubMed Web of Science ®Google Scholar
• Mateos M-V, Weisel K, Martin T, et al. Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice. Haematologica. 2023;108(8):2192–2204. doi: 10.3324/haematol.2022.280482
   PubMed Web of Science ®Google Scholar
• Martin T, Krishnan A, Yong K, et al. Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician’s choice of therapy in the flatiron health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma. EJHaem. 2022 Feb;3(1):97–108.
   PubMedGoogle Scholar
• Weisel K, Krishnan A, Schecter JM, et al. Matching-adjusted indirect treatment comparison to assess the comparative efficacy of ciltacabtagene autoleucel in CARTITUDE-1 versus Belantamab Mafodotin in DREAMM-2, selinexor-dexamethasone in STORM part 2, and Melphalan Flufenamide-dexamethasone in HORIZON for the treatment of patients with triple-class exposed relapsed or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):690–701.
   PubMed Web of Science ®Google Scholar
• Weisel K, Martin T, Krishnan A, et al. Comparative efficacy of Ciltacabtagene autoleucel in CARTITUDE-1 vs physician’s choice of therapy in the long-term follow-up of POLLUX, CASTOR, and EQUULEUS clinical trials for the treatment of patients with relapsed or refractory multiple myeloma. Clin Drug Investig. 2022 Jan;42(1):29–41.
   PubMed Web of Science ®Google Scholar
• Martin T, Usmani SZ, Schecter JM, et al. Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Curr Med Res Opin. 2021 Oct;37(10):1779–1788.
   PubMed Web of Science ®Google Scholar
• Hansen DK, Sidana S, Peres LC, et al. Idecabtagene vicleucel for relapsed/refractory multiple myeloma: real-world experience from the myeloma CAR T consortium. J Clin Oncol. 2023 Apr 10;41(11):2087–2097. doi: 10.1200/JCO.22.01365
   PubMed Web of Science ®Google Scholar
• Chakraborty R, Al Hadidi S. Intent matters: real-world applicability of idecabtagene vicleucel usage in the United States. J Clin Oncol. 2023 Jul 10;41(20):3657–3658. doi: 10.1200/JCO.23.00226
   PubMed Web of Science ®Google Scholar
• Sanoyan DA, Seipel K, Bacher U, et al. Real-life experiences with CAR T-cell therapy with idecabtagene vicleucel (ide-cel) for triple-class exposed relapsed/refractory multiple myeloma patients. BMC Cancer. 2023 Apr 15;23(1):345. doi: 10.1186/s12885-023-10824-3
   PubMed Web of Science ®Google Scholar
• Ferreri CJ, Hildebrandt MAT, Hashmi H, et al. Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. Blood Cancer J. 2023 Aug 9;13(1):117. doi: 10.1038/s41408-023-00886-8
   PubMed Web of Science ®Google Scholar
• Sidana S, Patel K, Peres L. Safety and efficacy of standard of care ciltacabtagene autoleucel (Cilts-cel) for relapsed/refractory multiple myeloma (RRMM): real world experience. Clin Lymphoma Myeloma Leuk. 2023;23:O–049. doi: 10.1016/S2152-2650(23)01667-1
   Web of Science ®Google Scholar
• Hayden PJ, Roddie C, Bader P, et al. Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA). Ann Oncol. 2022 Mar;33(3):259–275.
   PubMed Web of Science ®Google Scholar
• Cohen AD, Mateos MV, Cohen YC, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023 Jan 19;141(3): 219–230. doi: 10.1182/blood.2022015526
   Web of Science ®Google Scholar
• Cohen A, Einsele H, Delforge M, et al. Updated clinical data and biological correlative analyses of ciltacabtagene autoleucel (Cilta-cel) in lenalidomide-refractory multiple myeloma after 1–3 prior lines of therapy: CARTITUDE-2 cohort A. Clin Lymphoma Myeloma Leuk. 2022;22(S1):S1–S223 (abstr OAB-044). doi: 10.1016/S2152-2650(22)00318-4
   PubMedGoogle Scholar
• De Donk NW V, Agha M, Cohen AD, et al. Ciltacabtagene Autoleucel (cilta-cel), a BCMA-Directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2 cohort B 18-month follow-up. Blood. 2022;140(Supplement 1):7536–7537. doi: 10.1182/blood-2022-159169
   Google Scholar
• 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 Dec;27(12):2099–2103.
   PubMed Web of Science ®Google Scholar
• Cohen AD, Parekh S, Santomasso BD, et al. Incidence and management of CAR-T neurotoxicity in patients with multiple myeloma treated with ciltacabtagene autoleucel in CARTITUDE studies. Blood Cancer J. 2022 Feb 24;12(2):32. doi: 10.1038/s41408-022-00629-1
   PubMed Web of Science ®Google Scholar
• Graham CE, Lee WH, Wiggin HR, et al. Chemotherapy-induced reversal of ciltacabtagene autoleucel-associated movement and neurocognitive toxicity. Blood. 2023 Oct 5;142(14):1248–1252. doi: 10.1182/blood.2023021429
   PubMed Web of Science ®Google Scholar
• Gust J. BCMA-CAR T-cell treatment-associated parkinsonism. Blood. 2023 Oct 5;142(14):1181–1183. doi: 10.1182/blood.2023021860
   PubMed Web of Science ®Google Scholar
• Karschnia P, Miller KC, Yee AJ, et al. Neurologic toxicities following adoptive immunotherapy with BCMA-directed CAR T cells. Blood. 2023 Oct 5;142(14):1243–1248. doi: 10.1182/blood.2023020571
   PubMed Web of Science ®Google Scholar
• Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625–638.
   PubMed Web of Science ®Google Scholar
• Harrison SJ, Nguyen T, Rahman M, et al. CAR+ T-cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma. Blood. 2023;142(Supplement 1):6939. doi: 10.1182/blood-2023-178806
   Google Scholar
• Administration USFa D. FDA investigating serious risk of T-cell malignancy following BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. 2023. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous
   Google Scholar
• Rejeski K, Hansen DK, Bansal R, et al. The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma. J Hematol Oncol. 2023 Jul 31;16(1):88. doi: 10.1186/s13045-023-01465-x
   PubMed Web of Science ®Google Scholar
• Davis JA, Sborov DW, Wesson W, et al. Efficacy and safety of CD34+ stem cell boost for delayed hematopoietic recovery after BCMA directed CAR T-cell therapy. Transplant Cell Ther. 2023 Sep;29(9):567–571.
   PubMedGoogle Scholar
• Khan AN, Chowdhury A, Karulkar A, et al. Immunogenicity of CAR-T cell therapeutics: evidence, mechanism and mitigation. Front Immunol. 2022;13:886546. doi: 10.3389/fimmu.2022.886546
   PubMed Web of Science ®Google Scholar
• Sperling AS, Derman BA, Nikiforow S, et al. Updated phase I study results of PHE885, a T-Charge manufactured BCMA-directed CAR-T cell therapy, for patients (pts) with r/r multiple myeloma (RRMM). J Clin Oncol. 2023;41(16_suppl):abstr 8004. doi: 10.1200/JCO.2023.41.16_suppl.8004
   Google Scholar
• Prommersberger S, Reiser M, Beckmann J, et al. CARAMBA: a first-in-human clinical trial with SLAMF7 CAR-T cells prepared by virus-free sleeping beauty gene transfer to treat multiple myeloma. Gene Ther. 2021 Sep;28(9):560–571.
   PubMed Web of Science ®Google Scholar
• Cowan AJ, Pont MJ, Sather BD, et al. Gamma-secretase inhibitor in combination with BCMA chimeric antigen receptor T-cell immunotherapy for individuals with relapsed or refractory multiple myeloma: a phase 1, first-in-human trial. Lancet Oncol. 2023 Jul;24(7):811–822.
   PubMed Web of Science ®Google Scholar
• Banerjee R, Lee SS, Cowan AJ. Innovation in BCMA CAR-T therapy: building beyond the Model T. Front Oncol. 2022;12:1070353. doi: 10.3389/fonc.2022.1070353
   PubMed Web of Science ®Google Scholar
• Lin L, Cho S-F, Xing L, et al. Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma. Leukemia. 2021;35(3):752–763. doi: 10.1038/s41375-020-0951-5
   PubMed Web of Science ®Google Scholar
• Zhang M, Wei G, Zhou L, et al. GPRC5D CAR T cells (OriCAR-017) in patients with relapsed or refractory multiple myeloma (POLARIS): a first-in-human, single-centre, single-arm, phase 1 trial. Lancet Haematol. 2023 Feb;10(2):e107–e116.
   PubMed Web of Science ®Google Scholar
• Mailankody S, Devlin SM, Landa J, et al. GPRC5D-Targeted CAR T cells for myeloma. N Engl J Med. 2022 Sep 29;387(13):1196–1206. doi: 10.1056/NEJMoa2209900
   PubMed Web of Science ®Google Scholar
• Bal S, Berdeja J, Htut M, et al. BMS-986393 (CC-95266), a G protein-coupled receptor class c group 5 member D (GPRC5D)-targeted CAR T-cell therapy for relapsed/refractory multiple myeloma (RRMM): results from a phase 1 study. Hemasphere. 2023;7(S3):e9863287 (abstr S193) doi: 10.1097/01.HS9.0000967684.98632.87
   Google Scholar
• Mailankody S, Matous JV, Chhabra S, et al. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nat Med. 2023 Feb;29(2):422–429.
   PubMedGoogle Scholar
• Ahmed N, Shahzad M, Shippey E, et al. Socioeconomic and racial disparity in chimeric antigen receptor T cell therapy access. Transplant Cell Ther. 2022 Jul;28(7):358–364.
   PubMedGoogle Scholar
• Di M, Long JB, Isufi I, et al. Total costs of care during chimeric antigen receptor T-Cell therapy in patients with relapsed/refractory B cell Non-Hodgkin Lymphoma: a large Private insurance claim-based analysis. Blood. 2022;140(Supplement 1):10818–10819. doi: 10.1182/blood-2022-164915
   Google Scholar
• McDonald M, Bourjolly B, Shah S. CAR-T reimbursement in the US: ZS separates myths from reality. ZS Insights. 2022. https://www.cellandgene.com/doc/car-t-reimbursement-in-the-us-zs-separates-myths-from-reality-0001
   Google Scholar
• Sahli B, Eckwright D, Darling E, et al. Chimeric antigen receptor T-cell therapy real-world assessment of total cost of care and clinical events for the treatment of relapsed or refractory lymphoma. J Clin Oncol. 2021;39(suppl 15):e19500–e19500. doi: 10.1200/JCO.2021.39.15_suppl.e19500
   Web of Science ®Google Scholar
• Keating SJ, Gu T, Jun MP, et al. Health Care Resource Utilization and total costs of Care among patients with diffuse large B cell lymphoma treated with chimeric antigen receptor T cell Therapy in the United States. Transplant Cell Ther. 2022 Jul;28(7):e404 1–e404 6.
   Google Scholar
• Cliff ERS, Kelkar AH, Russler-Germain DA, et al. High cost of chimeric antigen receptor T-Cells: challenges and solutions. Am Soc Clin Oncol Educ Book. 2023 Jun;43(43):e397912.
   PubMedGoogle Scholar
• Palani HK, Arunachalam AK, Yasar M, et al. Decentralized manufacturing of anti CD19 CAR-T cells using CliniMACS Prodigy(R): real-world experience and cost analysis in India. Bone Marrow Transplant. 2023 Feb;58(2):160–167.
   PubMed Web of Science ®Google Scholar
• Prasad V. Immunotherapy: tisagenlecleucel - the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol. 2018 Jan;15(1):11–12. doi: 10.1038/nrclinonc.2017.156
   PubMed Web of Science ®Google Scholar
• Martinez-Cibrian N, Espanol-Rego M, Pascal M, et al. Practical aspects of chimeric antigen receptor T-cell administration: From commercial to point-of-care manufacturing. Front Immunol. 2022;13:1005457. doi: 10.3389/fimmu.2022.1005457
   PubMed Web of Science ®Google Scholar
• Juan M, Delgado J, Calvo G, et al. Is hospital exemption an alternative or a bridge to European medicines agency for developing academic chimeric antigen receptor T-Cell in Europe? Our experience with ARI-0001. Hum Gene Ther. 2021 Oct;32(19–20):1004–1007.
   PubMed Web of Science ®Google Scholar
• Jagannath S, Joseph N, Crivera C, et al. Component costs of CAR-T therapy in addition to treatment acquisition costs in patients with multiple myeloma. Oncol Ther. 2023 Jun;11(2):263–275.
   PubMed Web of Science ®Google Scholar
• Zhu F, Shah N, Xu H, et al. Closed-system manufacturing of CD19 and dual-targeted CD20/19 chimeric antigen receptor T cells using the CliniMACS prodigy device at an academic medical center. Cytotherapy. 2018 Mar;20(3):394–406.
   PubMed Web of Science ®Google Scholar
• D’Agostino M, Raje N. Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better? Leukemia. 2020;34(1):21–34. doi: 10.1038/s41375-019-0669-4
   PubMed Web of Science ®Google Scholar
• NWCJ VDD, Themeli M, SZ U. Determinants of response and mechanisms of resistance of CAR T-cell therapy in multiple myeloma. Blood Cancer Discov. 2021;2(4):302–318. doi: 10.1158/2643-3230.BCD-20-0227
   PubMedGoogle Scholar
• Rodriguez-Otero P, Prosper F, Alfonso A, et al. CAR T-Cells in multiple myeloma are ready for prime time. J Clin Med. 2020 Nov 6;9(11):3577. doi: 10.3390/jcm9113577
   PubMed Web of Science ®Google Scholar
• Berdeja JG, Madduri D, Usmani SZ, et al. Update of CARTITUDE-1: a phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma. J Clin Oncol. 2020;38(15_suppl):8505–8505. doi: 10.1200/JCO.2020.38.15_suppl.8505
   Web of Science ®Google Scholar
• Zudaire E, Madduri D, Usmani SZ, et al. Translational analysis from CARTITUDE-1, an ongoing phase 1b/2 study of JNJ-4528 BCMA-targeted CAR-T cell therapy in relapsed and/or refractory multiple myeloma (R/R MM), indicates preferential expansion of CD8+ T cell central memory cell subset. Blood. 2019;134(Supplement_1):928. doi: 10.1182/blood-2019-127309
   Google Scholar
• Garfall AL, Stadtmauer EA, Hwang WT. et al. Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight. 2019 Feb 21;4(4). doi: 10.1172/jci.insight.127684
   PubMed Web of Science ®Google Scholar
• Leblay N, Maity R, Barakat E, et al. Cite-Seq profiling of T cells in multiple myeloma patients undergoing BCMA targeting CAR-T or bites immunotherapy. Blood. 2020;136(Supplement 1):11. doi: 10.1182/blood-2020-137650
   PubMedGoogle Scholar
• Wang M, Pruteanu I, Cohen AD, et al. Identification and validation of predictive biomarkers to CD19- and BCMA-specific CAR T-cell responses in CAR T-cell precursors. Blood. 2019;134(Supplement_1):622. doi: 10.1182/blood-2019-122513
   Google Scholar
• Garfall AL, Dancy EK, Cohen AD, et al. T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma. Blood Adv. 2019 Oct 8;3(19):2812–2815. doi: 10.1182/bloodadvances.2019000600
   PubMed Web of Science ®Google Scholar
• Vià MC D, Dietrich O, Truger M, 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):616–619. doi: 10.1038/s41591-021-01245-5
   PubMed Web of Science ®Google Scholar
• Lee H, Ahn S, Maity R, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023 Sep;29(9):2295–2306.
   PubMed Web of Science ®Google Scholar
• Hamieh M, Dobrin A, Cabriolu A, et al. CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature. 2019 Apr;568(7750):112–116.
   PubMed Web of Science ®Google Scholar
• Gogishvili T, Danhof S, Prommersberger S, et al. SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7(+) normal lymphocytes. Blood. 2017 Dec 28;130(26):2838–2847. doi: 10.1182/blood-2017-04-778423
   PubMed Web of Science ®Google Scholar
• Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-Cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022 Dec 15;387(24):2232–2244. doi: 10.1056/NEJMoa2204591
   PubMed Web of Science ®Google Scholar
• Touzeau C, Schinke C, Minnema M, et al. Pivotal phase 2 Monumental-1 results of talqutamab (Tal), a GPRC5DxCD3 bispecific antibody (bsAb), for relapsed/refractory multiple Myeloma (MM). Hemasphere. 2023;7(S3):e5955094. (abstr S191) doi: 10.1097/01.HS9.0000967676.59550.94
   Google Scholar
• Bernabei L, Tian L, Garfall AL, et al. B-cell maturation antigen chimeric antigen receptor T-cell re-expansion in a patient with myeloma following salvage programmed cell death protein 1 inhibitor-based combination therapy. Br J Haematol. 2021 May;193(4):851–855.
   PubMed Web of Science ®Google Scholar
• Gay F, D’Agostino M, Giaccone L, et al. Immuno-oncologic approaches: CAR-T cells and checkpoint inhibitors. Clin Lymphoma Myeloma Leuk. 2017 Aug;17(8):471–478.
   PubMed Web of Science ®Google Scholar
• Mohyuddin GR, Atieh T, Ahmed N. et al. Intention to treat versus modified intention-to-treat analysis in B-cell maturation antigen and CD19 chimeric antigen receptor trials: a systematic review and meta-analysis. Eur J Cancer. 2021 Oct;156:164–174.
   PubMed Web of Science ®Google Scholar
• Bechman N, Maher J. Lymphodepletion strategies to potentiate adoptive T-cell immunotherapy - what are we doing; where are we going? Expert Opin Biol Ther. 2021 May;21(5):627–637. doi: 10.1080/14712598.2021.1857361
   PubMed Web of Science ®Google Scholar
• Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016 Jun 30;127(26):3321–30. doi: 10.1182/blood-2016-04-703751
   PubMed Web of Science ®Google Scholar
• Ludwig H, Terpos E, van de Donk N, et al. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European myeloma network. Lancet Oncol. 2023 Jun;24(6):e255–e269.
   PubMed Web of Science ®Google Scholar
• Jain MD, Smith M, Shah NN. How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood. 2023 May 18;141(20):2430–2442. doi: 10.1182/blood.2022017414
   PubMed Web of Science ®Google Scholar