Overview of Approved CAR-T Therapies, Ongoing Clinical Trials, and Its Impact on Clinical Practice

Overview

Journal EJHaem

Specialty Hematology

Date 2022 Jul 18

PMID 35844299

Authors

Salyka Sengsayadeth

Bipin N Savani

Olalekan Oluwole

Bhagirathbhai Dholaria

Affiliations

Soon will be listed here.

Abstract

In recent years, we have seen rapid expansion of chimeric antigen receptor T-cell (CAR-T) therapies in multiple malignancies. CAR-T therapy has profoundly altered the treatment landscape of non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. Currently available CD19 and B-cell maturation antigen-directed CAR-T therapies have shown high overall response rate and durable remissions in patients who have failed standard therapies. Multiple studies are underway exploring the role of CAR-T-cell therapy as earlier line of treatment. In high-grade B-cell lymphoma, CD19 CAR-T therapy may replace autologous hematopoietic cell transplantation as second line therapy in near future. CAR-T-cell therapy targeting novel tumor-associated antigens will help expand utility of this treatment modality in other hematological malignancies. It may also help overcome limitations of currently approved CAR-T-cell therapies. In this review, we have provided an overview of currently approved CAR-T therapies and upcoming clinical trials which may potentially impact the clinical practice.

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References

Maude S, Laetsch T, Buechner J, Rives S, Boyer M, Bittencourt H . Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5):439-448. PMC: 5996391. DOI: 10.1056/NEJMoa1709866. View

Liu M, Deng H, Mu J, Li Q, Pu Y, Jiang Y . Ibrutinib improves the efficacy of anti-CD19-CAR T-cell therapy in patients with refractory non-Hodgkin lymphoma. Cancer Sci. 2021; 112(7):2642-2651. PMC: 8253282. DOI: 10.1111/cas.14915. View

Abramson J, Palomba M, Gordon L, Lunning M, Wang M, Arnason J . Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020; 396(10254):839-852. DOI: 10.1016/S0140-6736(20)31366-0. View

Munshi N, Anderson Jr L, Shah N, Madduri D, Berdeja J, Lonial S . Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021; 384(8):705-716. DOI: 10.1056/NEJMoa2024850. View

Locke F, Ghobadi A, Jacobson C, Miklos D, Lekakis L, Oluwole O . Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2018; 20(1):31-42. PMC: 6733402. DOI: 10.1016/S1470-2045(18)30864-7. View

Gauthier J, Hirayama A, Purushe J, Hay K, Lymp J, Li D . Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood. 2020; 135(19):1650-1660. PMC: 7205814. DOI: 10.1182/blood.2019002936. View

Jain P, Nastoupil L, Westin J, Lee H, Navsaria L, Steiner R . Outcomes and management of patients with mantle cell lymphoma after progression on brexucabtagene autoleucel therapy. Br J Haematol. 2020; 192(2):e38-e42. DOI: 10.1111/bjh.17197. View

Savani M, Oluwole O, Dholaria B . New targets for CAR T therapy in hematologic malignancies. Best Pract Res Clin Haematol. 2021; 34(3):101277. DOI: 10.1016/j.beha.2021.101277. View

Neelapu S, Locke F, Bartlett N, Lekakis L, Miklos D, Jacobson C . Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017; 377(26):2531-2544. PMC: 5882485. DOI: 10.1056/NEJMoa1707447. View

10.

Schuster S, Tam C, Borchmann P, Worel N, McGuirk J, Holte H . Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021; 22(10):1403-1415. DOI: 10.1016/S1470-2045(21)00375-2. View

11.

Ramos C, Grover N, Beaven A, Lulla P, Wu M, Ivanova A . Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2020; 38(32):3794-3804. PMC: 7655020. DOI: 10.1200/JCO.20.01342. View

12.

Wang M, Munoz J, Goy A, Locke F, Jacobson C, Hill B . KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N Engl J Med. 2020; 382(14):1331-1342. PMC: 7731441. DOI: 10.1056/NEJMoa1914347. View

13.

Shah N . Advances in CAR T-cell therapy for the treatment of multiple myeloma. Clin Adv Hematol Oncol. 2020; 18(6):316-318. View

14.

Pan J, Tan Y, Wang G, Deng B, Ling Z, Song W . Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial. J Clin Oncol. 2021; 39(30):3340-3351. DOI: 10.1200/JCO.21.00389. View

15.

Nastoupil L, Jain M, Feng L, Spiegel J, Ghobadi A, Lin Y . Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. J Clin Oncol. 2020; 38(27):3119-3128. PMC: 7499611. DOI: 10.1200/JCO.19.02104. View

16.

Sengsayadeth S, Savani B, Oluwole O, Dholaria B . Overview of approved CAR-T therapies, ongoing clinical trials, and its impact on clinical practice. EJHaem. 2022; 3(Suppl 1):6-10. PMC: 9175669. DOI: 10.1002/jha2.338. View

17.

Jagannath S, Lin Y, Goldschmidt H, Reece D, Nooka A, Senin A . KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma. Blood Cancer J. 2021; 11(6):116. PMC: 8213772. DOI: 10.1038/s41408-021-00507-2. View

18.

Shah B, Ghobadi A, Oluwole O, Logan A, Boissel N, Cassaday R . 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. PMC: 11613962. DOI: 10.1016/S0140-6736(21)01222-8. View

19.

Schuster S, Bishop M, Tam C, Waller E, Borchmann P, McGuirk J . Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018; 380(1):45-56. DOI: 10.1056/NEJMoa1804980. View

20.

Sallman D, Brayer J, Sagatys E, Lonez C, Breman E, Agaugue S . NKG2D-based chimeric antigen receptor therapy induced remission in a relapsed/refractory acute myeloid leukemia patient. Haematologica. 2018; 103(9):e424-e426. PMC: 6119132. DOI: 10.3324/haematol.2017.186742. View