Autologous chimeric antigen receptor (CAR)-T cell therapy has transformed the management options for patients with refractory/relapsed (r/r) B-cell cancers including acute lymphoblastic leukaemia (ALL),¹ large B-cell lymphoma (LBCL) ^2–4 and myeloma,^{5 6} and six CAR-T cell therapy products have now been FDA-approved. CAR-T is increasingly being investigated in earlier therapeutic lines for hematological malignancy,⁷ solid cancers,⁸ and now is finding clinical value in autoimmune disease.⁹

Here we discuss the science of CAR-T cell therapy including design, manufacture, and clinical development in the hematology space to set the scene for the transformative impacts of this therapy in autoimmunity.

References

1. Shah BD, Ghobadi A, Oluwole OO, 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;398(10299):491–502. doi: 10.1016/s0140-6736(21)01222-8.

2. 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;377(26):2531–44. doi: 10.1056/NEJMoa1707447.

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

4. 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;396(10254):839–52. doi: 10.1016/s0140-6736(20)31366-0.

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

6. 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):314–24. doi: 10.1016/s0140-6736(21)00933-8.

7. Neelapu SS, Dickinson M, Munoz J, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: The Phase 2 ZUMA-12 trial. Nat Med. 2022;28(4):735–42. doi: 10.1038/s41591-022-01731-4.

8. Del Bufalo F, De Angelis B, Caruana I, et al. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. N Engl J Med. 2023;388(14):1284–95. doi: 10.1056/NEJMoa2210859.

9. Müller F, Taubmann J, Bucci L, et al. CD19 CAR T-cell therapy in autoimmune disease - A case series with follow-up. N Engl J Med. 2024;390(8):687–700. doi: 10.1056/NEJMoa2308917.

Learning Objectives At the end of this presentation participants will be able to:

• Discuss the scientific design, manufacturing process, and clinical development of CAR-T cells, particularly for treating hematological malignancies

• Explain the rationale for using CAR-T therapy in autoimmune diseases based on its success in treating blood cancers