CAR-T CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA CAR-T and CLL

Main Article Content

Ugo Testa
Dr. Elvira Pelosi
Dr. Germana Castelli
Dr. Alberto Fresa
Prof. Luca Laurenti

Keywords

Chronic Lymphoid Leukemia; CLLia, CAR-T Cells; CLL relapsed/refractory

Abstract

The treatment outcomes of patients with chronic lymphocytic leukemia (CLL) have considerably improved with the introduction of targeted therapies based on Bruton kinase inhibitors (BTKIs), venetoclax, and anti-CD20 monoclonal antibodies. However, despite these consistent improvements, patients who become resistant to these agents have poor outcomes and need new and more productive therapeutic strategies.


Among these new treatments, a potentially curative approach consists of the use of chimeric antigen receptor T (CAR-T) cell therapy, which achieved remarkable success in various B-cell malignancies, including B-cell Non-Hodgkin Lymphomas (NHLs) and B-acute lymphoblastic Leukemia (ALL). However, although CAR-T cells were initially used for the treatment of CLL, their efficacy in CLL patients was lower than in other B-cell malignancies. This review analyses the possible mechanisms of these failures. It highlights some recent developments that could offer the perspective of the incorporation of CAR-T cells in treatment protocols for relapsed/refractory CLL patients.


Keywords: Chronic Lymphoid Leukemia; CLL; CAR-T Cells; Relapsed/resistant CLL:

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References

1) SEER Cancer Stat Facts: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/statfacts/html/cllsll.html
2) Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(1):23-33. doi:10.1016/j.annonc.2020.09.019
3) NCCN Guidelines Update: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Natl Compr Canc Netw. 2023;21(5.5):563-566. doi:10.6004/jnccn.2023.5007
4) Lew TE, Lin VS, Cliff ER, Blombery P, Thompson ER, Handunnetti SM, Westerman DA, Kuss BJ, Tam CS, Huang D, et al. Outcomes of patients with CLL sequentially resistant to both BCL2 and BTK inhibition. Blood Adv 2021; 5: 4054-4063.
5) Mato, A.R.; Hess, L.M.; Chen, Y.; Abada, P.B.; Konig, H.; Pagel, J.M.; Walgren, R. Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) Previously Treated With Both a Covalent BTK and BCL2 Inhibitor in the United States: A Real-World Database Study. Clin. Lymphoma Myeloma Leuk. 2023, 23, 57–67.
6) Eyre, T.A.; Hess, L.M.; Sugihara, T.; He, D.; Khanal, M.; Pagel, J.M.; Walgren, R.; Abada, P.B.; Konig, H.; Roeker, L.; Mato, A. Clinical outcomes among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who received treatment with a covalent BTK and BCL2 inhibitor in the United States: A real-world database study. Leuk. Lymphoma 2023, 64, 1005-1016.
7) Innocenti I, Fresa A, Tomasso A, Tarnani M, De Padua L, Benintende G, Pasquale R, Galli E, Morelli F, Giannarelli D, Autore F, Laurenti L. Treatment Sequencing and Outcome of Chronic Lymphocytic Leukemia Patients Treated at Fondazione Policlinico Universitario Agostino Gemelli IRCCS: A Thirty-Year Single-Center Experience. Cancers (Basel). 2023 Nov 26;15(23):5592. doi: 10.3390/cancers15235592. PMID: 38067296; PMCID: PMC10705134.
8) Roeker LE, Dreger P, Brown JR, Lahoud OB, Eyre TA, Brander DM, et al. Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents. Blood Adv [Internet]. 2020 Aug 25;4(16):3977–89. Available from: https://doi.org/10.1182/bloodadvances.2020001956
9) Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, 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. Epub 2017 Dec 10. PMID: 29226797; PMCID: PMC5882485.
10) Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):91-103. doi: 10.1016/S1470-2045(21)00591-X. Epub 2021 Dec 8. PMID: 34895487.
11) Locke FL, Miklos DB, Jacobson CA, Perales MA, Kersten MJ, Oluwole OO, et al; All ZUMA-7 Investigators and Contributing Kite Members. 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. Epub 2021 Dec 11. PMID: 34891224.
12) Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, 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. PMID: 32242358; PMCID: PMC7731441.
13) Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, et al. KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study. Lancet. 2021 Aug 7;398(10299):491-502. doi: 10.1016/S0140-6736(21)01222-8. Epub 2021 Jun 4. PMID: 34097852.
14) Abramson JS, Solomon SR, Arnason J, Johnston PB, Glass B, Bachanova V, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023 Apr 6;141(14):1675-1684. doi: 10.1182/blood.2022018730. PMID: 36542826; PMCID: PMC10646768.
15) Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, 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. Epub 2020 Sep 1. PMID: 32888407.
16) 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 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866. PMID: 29385370; PMCID: PMC5996391.
17) Mueller KT, Waldron E, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, et al. Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia. Clin Cancer Res. 2018 Dec 15;24(24):6175-6184. doi: 10.1158/1078-0432.CCR-18-0758. Epub 2018 Sep 6. PMID: 30190371; PMCID: PMC7433345.
18) Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al; JULIET Investigators. 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. Epub 2018 Dec 1. PMID: 30501490.
19) Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022 Feb;28(2):325-332. doi: 10.1038/s41591-021-01622-0. Epub 2021 Dec 17. PMID: 34921238.
20) Sommermeyer D, Hudecek M, Kosasih PL, Gogishvili T, Maloney DG, Turtle CJ, Riddell SR. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2016 Feb;30(2):492-500. doi: 10.1038/leu.2015.247. Epub 2015 Sep 15. PMID: 26369987; PMCID: PMC4746098
21) Turtle CJ, Hay KA, Hanafi LA, Li D, Cherian S, Chen X, Wood B, Lozanski A, Byrd JC, Heimfeld S, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib. J Clin Oncol 2017; 35: 3010-3020.
22) Liang E, Hirayama A, Kimble E, Portuguese, Albittar A, Chapouis A, Shadman M, Till B, Cassaday R, Milano F, et al. Long-term follow-up update and multivariable analyses of factors associated with duration of response after CD19 CAR T-cell therapy for relapsed/refractory CLL. Hemasphere 2023; 7 (suppl.1): e472395b.
23) Siddiqi T, Soumarai JD, Wierda WG, D ubovsky JA, Gillenwater HH, Pharm LG, Mitchell A, Thorpe J, Yang LDorritie KA, et al. Rapid MRD-negative responses in patients with relapsed/refractory CLL treated with Liso-Cel, a CD19-directed CAR T-cell product: preliminary results from transcend CLL 004, a phase 1 / 2 study including patients with high-risk disease previously treated with ibrutinib. Blood 2018; 132 (suppl. 1):300.
24) Siddiqi T, Soumerai JD, Dorritie KA, Stephens DM, Riedell PA, Arnason JA, Kipps TJ, Gillenwater HH, Gong L, Yang L, et al. Phase 1 TRASCEND CELL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood 2022; 139: 1794-1806.
25) Siddiqi T, Maloney D, Kenderian SS, Brander DM, Dorritie K, Soumerai J. Lisocabtagene maraleucel in chronic lymphocytic leukemia and small lymphocytic lymphoma (TRASCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet 2023; 402: 641-654.
26) Siddiqi T, Maloney DG, Kenderian SS, Brander DM, Dorritie K, Soumnerai J, Riedell PA, Shah NV, Nath R, Fakhri B, et al. Lisocabtagene Maraleucel (liso-cel) in R/R CLL/SLL: 24-median follow-up of TRASCEND CLL-004. Blood 2023; 142 (suppl.1): 330.
27) Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, Samanta M, Lakhal M, Gloss B, Danet-Desnoyers G, Campana D, Riley JL, Grupp SA, June CH. 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. doi: 10.1038/mt.2009.83. Epub 2009 Apr 21. Erratum in: Mol Ther. 2015 Jul;23(7):1278. PMID: 19384291; PMCID: PMC2805264.
28) Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl 2015; 7: 303ra139.
29) Frey NV, Gill S, Hexner EO, Schuster S, Nasta S, Loren A, Svoboda J, Stadtmauer E, Landsburg DJ, Mato A, et al. Long-term outcomes from a randomized dose optimization study of chimeric antigen receptor modified T cells in relapsed chronic lymphocytic leukemia. J Clin Oncol 2020; 38: 2862-2871.
30) Melenhorst JJ, Chen GM, Wang M, Porter DL, Chen C, Collins MA, Gao P, Brabyopadhyay S, n H, Zhao Z, et al. Decade-long leukemia remissions with persistence of CD4+ CAR T cells. Nature 2022; 602: 503-509.
31) Wang M, Munoz J, Goy A, Locke FL, Jacobson CA, Hill BT, Timmerman JM, Holmes H, Jaglowski S, Flinn IW, McSweeney PA, Miklos DB, Pagel JM, Kersten MJ, Milpied N, Fung H, Topp MS, Houot R, Beitinjaneh A, Peng W, Zheng L, Rossi JM, Jain RK, Rao AV, Reagan PM. 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. PMID: 32242358; PMCID: PMC7731441.
32) Flinn I, Marris M, Wierda WG, Coutre S, Pagel JM, Byrd JC, Goyal L, Goodman K, Zheng Y, Milletti F, et al. ZUMA-8: a phase 1-2 multicenter study evaluating KTE-X19 in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). J Clin Oncol 2019; 37(suppl. 16): TPS7566.
33) Davids MS, Kenderian SS, Flinn IW, Hill BT, Maris M, Ghia P, Byrne M, Barlett NL, Pagel JM, Zheng Y, et al. ZUMA-8: a phase 1 study of KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory chronic lymphocytic leukemia. Blood 2022; 140 (suppl. 1): 7454-7456.
34) Kochenderfer JN, Feldman SA, Zhao Y, Xu H, Black MA, Morgan RA, Wilson WH, Rosenberg SA. Construction and preclinical evaluation of an anti-CD19 chimeric antigen receptor. J Immunother. 2009 Sep;32(7):689-702. doi: 10.1097/CJI.0b013e3181ac6138. PMID: 19561539; PMCID: PMC2747302.
35) Kochenderfer JN, Dudley ME, Kassim SH, Somerville R, Carpenter RO, Setler-Stevenson M, Yang JC, Phan GQ, Hughes MS, Sherry RM, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol 2015; 33: 540-549.
36) Cappell KM, Sherry RM, Yang JC, Goff SL, Vanasse DA, McInntyre L, Rosenberg SA, Kochenderfer JN. Long-term follow-up of anti-CD19 chimeric antigen receptor T-cell therapy. J Clin Oncol 2020; 38: 3805-3815.
37) Martinez-Cibrian N, Betriu S, Ortiz-Maldonado V, Esteban D, Tovar N, Moreno AT, Alserawan L; Montoro M, Van Muyden A, Pont M, et al. Initial clinical results of EUPLAGIA-1, a phase 1-2 trial of point-of-care manufactured GLPG5201 in R/R CLL/SLL with or without Richter’s transformation. Hemasphere 2023; 7(S3): 2714-2715.
38) Tovar N, Ortiz-Maldonado V, Martinez-Cibrian N, Betriu S, Esteban D, Triguero A, Verbruggen N, Spoon M, Liefaard MC, Pont M, van Muyden A. Seven-day vein-tovein point-of-care manufactured CD19 CAR T cells (GLPG5201) in relapsed/refractory CLL/SLL including Richter’s transformation: results from the phase 1 Euplagia-1 trial. Blood 2023; 142 (suppl.1): 2112.
39) Ortiz-Maldonado V, Martinez-Cibrian N, Del Campo Balguerias G, Espanol-Rego M, Navarro S, Lopez-Oreja I, Nadeu F, Cobo A, Brillembourg H, Alserawan L, et al. Varnicambtagene autoleucel (ARI-0001) for relapsed or refractory chronic lymphocytic leukemia (CLL) and Richter transformation (RT). Blood 2023 142 (suppl.1): 3483.
40) Douglas M. Richter transformation: clinical manifestations, evaluation, and management. J Adv Pract Oncol 2022; 13: 525-534.
41) Benjamini O, Shimoni A, Besser M, Shem-Tov N, Danylesko I, Yerushalmi R, Merkel DG, Tadmor T, Lavie D, et al. Safety and efficacy of CD19-CAR T cells in Richter’s transformation after targeted therapy for chronic lymphocytic leukemia. Blood 2020; 136(suppl.1): 40.
42) Kittai AS, Bond DA, William B, Saad A, Penza S, Efebera Y, Larkin K, Wall SA, Choe HK, Bhatnagar B, et al. Clinical activity of axicabtagene ciloleucel in adult patients with Richter syndrome. Blood Adv 2020; 4: 4648-4652.
43) Bensaber H, Bachy E, Beauvais D, Dulery R, Gastinne T, Villemagne B, Roulin L, Paubelle E, Castilla-Llorente C, Longval T, et al. Anti-CD19 CAR T-cell therapy for patients with Richter syndrome: a Lysa study from the Descar-T registry. Blood 2022; 140 (suppl.1): 3803-3804.
44) Blackmon A, Danilov AV, Wang L, Pillai R, rshkarlo HB, Rosen ST, Siddiqi T. Richter’s transformation after CD-19 directed CAR-T cells for relapsed/refractory chronic lymphocytic leukemia (CLL). Blood 2021; 138 (suppl. 1): 1430.
45) Long M, Beckwith K, Do P, Mundy BL, Gordon A, Lehman AM, Maddocks KJ, Cheney C, Jones JA, et al. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest 2017; 127: 3052-3064.
46) Fraietta JA, Beckwith KA, Patel PR, Ruella M, Zheng Z, Barrett DM, Lacey SF, Melenhorst J, McGettigan SE, et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood 2016; 127: 1117-1127.
47) Ruella M, Kenderian SS, Shestova O, ichinsky M, Melenhorst JJ, Wasik MA, Lacey SF, June CH, Gill S, et al. Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms. Leukemia 2017; 31: 246-248.
48) Papazoglou D, Wang XV, Shanafelt TD, Lesnick CE, Ioannou N, De Rossi G, Herter S, Bacac M, Klein C, Tallman MS, Kay NE, Ramsay AG. Ibrutinib-based therapy reinvigorates CD8+ T cells compared to chemoimmunotherapy: immune monitoring from the E1912 trial. Blood. 2024 Jan 4;143(1):57-63. doi: 10.1182/blood.2023020554. PMID: 37824808; PMCID: PMC10797553.
49) Gauthier J, Hirayama AV, Purushe J, Hay KA, Lymp J, Li DH, Yeung C, Sheih A, Pender BS, Hawkins RM, et al. Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood 2020; 135: 1650-1660.
50) Gill S, Vides V, Frey NV, Hexner EO, Metzeger S, O’Brien M, Hwang WT, Brogdon JL, Davis MM, Fraietta JA, et al. Anti-CD10 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv 2022; 6: 5774-5781.
51) Vitale C, Griggio V, Perutelli F, Coscia M. CAR-modified cellular therapies in chronic lymphocytic leukemia: is the uphili road getting less steep? HemaSphere 2023; 7: 12(e988).
52) Fraietta JA, Lacey SF, Orlando EJ, Pruteanu-Malinci I, Gohil M, Lundh S, Boesteanu AC, Wang Y, O’Connor RS, Hwang WT, et al. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 2018; 24: 563-571.
53) Van Bruggen J, Martens A, Fraietta JA, Hofland T, Tonino SAH, Eldering E, Levin MD, Siska PJ, Endstra S, Rathmell JC, et al.
54) Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA, Reich TJ, Cogdill AP, Morrissette J, De Nizio JE, Reddy S, et al.
55) Nobles CL, Sherill-Mix S, Everett JK, Reddy S, Fraietta JA, Porter DL, Frey N, Gill S, Grupp SA, Maude SL, et al. CD19-targeting CAR T cell immunotherapy outcomes correlate with genomic modification by vector integration. J Clin Invest 2020; 130: 673-685.
56) Kong W, Dimitri A, Wang W, Jung IY, Ott CJ, Fasolino M, Wang Y, Kulikovskaya I, Gupta M, Yoder T, et al. BET bromodomain protein inhibition reverses chimeric antigen receptor chimeric antigen receptor extinction and reinvigorates exhausted T cells in chronic lymphocytic leukemia. J Clin Invest 2021; 13: e145459.
57) Agarwal S, Aznar MA, Rech AJ, Good CR, Kuramitsu S, Da T, Gahil M, Chen L, Hong SJ, Ravikumur S, et al. Deletion of the co-inhibitory co-receptor CTLA4 enhances and invigorates chimer antigen receptor T cells. Immunity 2023; 56: 1-20.
58) Shadman M,Yeung CC, Redman M, Lee SY, Lee DH, Ra S, Ujjani CS, Dezube BJ, Poh C, Warren EH, et al. High efficacy and low toxicity of MB-106, a third generation CD20 targeted CAR-T for treatment of relapsed/refractory b-NHL and CLL. Transplant Cell Ther 2022; 28: S182-S183.
59) Shah NN, Johnson BD, Schneider D, Zhu F, Szabo A, Keever-Taylor CA, Krueger W, Worden AA, Kadan MJ, Yim S.; et al. Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose-escalation and expansion trial. Nat Med 2020; 26: 1569-1575.
60) Tong C, Zhang Y, Liu Y, Ji X, Zhang WY, Guo Y, Han X, Ti D, Dai H, Wang C., et al. Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B cell lymphoma. Blood 2020; 136: 1632-1644.
61) Park JH, Palomba ML, Bellevi CL, Riviere I, Wang X, Senechal B, Furman RR, Bernal Y, Hall M, Pineda J, et al. A phase I first-in-human clinical trial of CD19-targeted 19-28z/4-1BBL “Armored” CAR T cells in aptients with relapsed or refractory NHL and CLL including Richter’s transformation. Blood 2018; 132(suppl.1): 224.
62) Benjamin R, Jain N, Maus MV, Boissel N, Graham C, Jorwik A, Yallop D, Konopleva M, Frigault MJ, Teshima T, et al. UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (CALM): a phase 1, dose-escalation trial. Lancet Haematol 2022; 9: e833-e843.
63) Dupouy S, Marciq I, Derippe T, Almena-Carrasco M, Jozwik A, Fouliard S, Adimy Y, Geronimi J, Graham C, Jain N, et al. Clinical pharmacology and determinants of response to UCART19, an allogeneic anti-CD19 CAR-T cell product, in adult B-cell acute lymphoblastic leukemia. Cancer Res commun 2022; 2: 1520-1530.
64) Brudno JN, Sommerville R, Shi V, Rose J, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stem cell transplantation without causing graft-versus-host disease. J Clin Oncol 2016; 344: 1112-1121.
65) Brezinger-Dayan K, Itzhaki O, Melnichenko J, Kubi A, Zelter L, Jacoby E, Avigdot A, Shapira Frommer R, Besser MJ. Impact of cryopreservation on CAR T production and clinical response. Front Oncol 2022; 12: 1024362.
66) Kutsch N, Godel P, Voltin CA, Hallek M, Scheid C, Borchmann P, Holtick U. Long-term remission in a patient with relapsed Richter’s transformation treated with CD19-directed chimeric antigen-receptor T-cells after allogeneic stem cell transplantation. Eur J Haematol 2024; in press.
67) Markl F, Schultheib C, Ali M, Chen SS, Zintchenko M, Egli L, Mietz J, Chijioke D, Paschold L, Spajic S, et al. Mutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemia. Nat Commun 2024; 15: 993.