Dynamics of Immune Reconstitution and Impact on Outcomes Across CAR-T Cell Products in Large B-cell Lymphoma

Overview

Journal Blood Cancer Discov

Specialties Hematology
Oncology

Date 2024 Dec 12

PMID 39666878

Authors

Danny Luan

Susan DeWolf

Teng Fei

Sandeep Raj

Gunjan L Shah

Caleb A Lareau

Mohammad Alhomoud

Gilles Salles

Alfredo Rivas-Delgado

Kai Rejeski

Jae H Park

Efrat Luttwak

Alejandro Luna de Abia

Magdalena Corona

Evangelos Ntrivalas

Giulio Cassanello

Marina Gomez-Llobell

Allison Parascondola

Michael Scordo

Katharine C Hsu

M Lia Palomba

Miguel-Angel Perales

Roni Shouval

Affiliations

Soon will be listed here.

Abstract

This study reveals differences in IR patterns after CAR-T therapy in patients with large B-cell lymphoma, with early NK cell recovery emerging as a key predictor of survival. These findings provide potential future avenues of research for improving patient outcomes and tailoring post-therapy management strategies to mitigate relapse risk.

References

Hassan R, Butler M, OCearbhaill R, Oh D, Johnson M, Zikaras K . Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results. Nat Med. 2023; 29(8):2099-2109. PMC: 10427427. DOI: 10.1038/s41591-023-02452-y. View

Sterner R, Sterner R . CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021; 11(4):69. PMC: 8024391. DOI: 10.1038/s41408-021-00459-7. View

Minculescu L, Marquart H, Friis L, Petersen S, Schiodt I, Ryder L . Early Natural Killer Cell Reconstitution Predicts Overall Survival in T Cell-Replete Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016; 22(12):2187-2193. DOI: 10.1016/j.bbmt.2016.09.006. View

Min B . Spontaneous T Cell Proliferation: A Physiologic Process to Create and Maintain Homeostatic Balance and Diversity of the Immune System. Front Immunol. 2018; 9:547. PMC: 5868360. DOI: 10.3389/fimmu.2018.00547. View

Wudhikarn K, Perales M . Infectious complications, immune reconstitution, and infection prophylaxis after CD19 chimeric antigen receptor T-cell therapy. Bone Marrow Transplant. 2022; 57(10):1477-1488. PMC: 9285870. DOI: 10.1038/s41409-022-01756-w. View

Caimi P, Pacheco Sanchez G, Sharma A, Otegbeye F, Ahmed N, Rojas P . Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Front Immunol. 2021; 12:745320. PMC: 8546323. DOI: 10.3389/fimmu.2021.745320. View

Ghilardi G, Chong E, Svoboda J, Wohlfarth P, Nasta S, Williamson S . Bendamustine is safe and effective for lymphodepletion before tisagenlecleucel in patients with refractory or relapsed large B-cell lymphomas. Ann Oncol. 2022; 33(9):916-928. PMC: 11332249. DOI: 10.1016/j.annonc.2022.05.521. View

Ayala Ceja M, Khericha M, Harris C, Puig-Saus C, Chen Y . CAR-T cell manufacturing: Major process parameters and next-generation strategies. J Exp Med. 2024; 221(2). PMC: 10791545. DOI: 10.1084/jem.20230903. View

Marofi F, Saleh M, Rahman H, Suksatan W, Al-Gazally M, Abdelbasset W . CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies. Stem Cell Res Ther. 2021; 12(1):374. PMC: 8252313. DOI: 10.1186/s13287-021-02462-y. View

10.

Williams K, Hakim F, Gress R . T cell immune reconstitution following lymphodepletion. Semin Immunol. 2007; 19(5):318-30. PMC: 2180244. DOI: 10.1016/j.smim.2007.10.004. View

11.

van den Brink M, Velardi E, Perales M . Immune reconstitution following stem cell transplantation. Hematology Am Soc Hematol Educ Program. 2015; 2015:215-9. DOI: 10.1182/asheducation-2015.1.215. View

12.

Chong E, Ruella M, Schuster S . Five-Year Outcomes for Refractory B-Cell Lymphomas with CAR T-Cell Therapy. N Engl J Med. 2021; 384(7):673-674. DOI: 10.1056/NEJMc2030164. View

13.

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

14.

Rejeski K, Jain M, Shah N, Perales M, Subklewe M . Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management. Lancet Haematol. 2024; 11(6):e459-e470. DOI: 10.1016/S2352-3026(24)00077-2. View

15.

Logue J, Zucchetti E, Bachmeier C, Krivenko G, Larson V, Ninh D . Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica. 2020; 106(4):978-986. PMC: 8017820. DOI: 10.3324/haematol.2019.238634. View

16.

Yanez L, Sanchez-Escamilla M, Perales M . CAR T Cell Toxicity: Current Management and Future Directions. Hemasphere. 2019; 3(2):e186. PMC: 6746032. DOI: 10.1097/HS9.0000000000000186. View

17.

Lickefett B, Chu L, Ortiz-Maldonado V, Warmuth L, Barba P, Doglio M . Lymphodepletion - an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle. Front Immunol. 2024; 14:1303935. PMC: 10770848. DOI: 10.3389/fimmu.2023.1303935. View

18.

Wang W, Liu Y, He Z, Li L, Liu S, Jiang M . Breakthrough of solid tumor treatment: CAR-NK immunotherapy. Cell Death Discov. 2024; 10(1):40. PMC: 10799930. DOI: 10.1038/s41420-024-01815-9. View

19.

Hill J, Seo S . How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020; 136(8):925-935. PMC: 7441168. DOI: 10.1182/blood.2019004000. View

20.

Maude S, Frey N, Shaw P, Aplenc R, Barrett D, Bunin N . Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371(16):1507-17. PMC: 4267531. DOI: 10.1056/NEJMoa1407222. View