Long-term Follow-up of CD19-CAR T-cell Therapy in Children and Young Adults with B-ALL

Overview

Journal Hematology Am Soc Hematol Educ Program

Specialty Hematology

Date 2023 Dec 9

PMID 38066902

Authors

Rebecca Epperly

Nirali N Shah

Affiliations

Soon will be listed here.

Abstract

The tremendous successes of CD19-directed CAR T cells in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) has led to the more widespread use of this important treatment modality. With an ability to induce remission and potentially lead to long-term survival in patients with multiply relapsed/chemotherapy refractory disease, more children are now receiving this therapy with the hope of inducing a long-term durable remission (with or without consolidative hematopoietic cell transplantation). While overcoming the acute toxicities was critical to its broad implementation, the emerging utilization requires close evaluation of subacute and delayed toxicities alongside a consideration of late effects and issues related to survivorship following CAR T cells. In this underexplored area of toxicity monitoring, this article reviews the current state of the art in relationship to delayed toxicities while highlighting areas of future research in the study of late effects in children and young adults receiving CAR T cells.

Citing Articles

Late complications and long-term care of adult CAR T-cell patients.

Bishop M Hematology Am Soc Hematol Educ Program. 2024; 2024(1):109-115.

PMID: 39643985 PMC: 11665735. DOI: 10.1182/hematology.2024000534.

References

Summers C, Wu Q, Annesley C, Bleakley M, Dahlberg A, Narayanaswamy P . Hematopoietic Cell Transplantation after CD19 Chimeric Antigen Receptor T Cell-Induced Acute Lymphoblastic Lymphoma Remission Confers a Leukemia-Free Survival Advantage. Transplant Cell Ther. 2021; 28(1):21-29. DOI: 10.1016/j.jtct.2021.10.003. View

Zver T, Frontczak S, Poirot C, Rives-Feraille A, Leroy-Martin B, Koscinski I . Minimal residual disease detection by multicolor flow cytometry in cryopreserved ovarian tissue from leukemia patients. J Ovarian Res. 2022; 15(1):9. PMC: 8767661. DOI: 10.1186/s13048-021-00936-4. View

Fried S, Avigdor A, Bielorai B, Meir A, Besser M, Schachter J . Early and late hematologic toxicity following CD19 CAR-T cells. Bone Marrow Transplant. 2019; 54(10):1643-1650. DOI: 10.1038/s41409-019-0487-3. View

Deya-Martinez A, Alonso-Saladrigues A, Garcia A, Faura A, Torrebadell M, Vlagea A . Kinetics of humoral deficiency in CART19-treated children and young adults with acute lymphoblastic leukaemia. Bone Marrow Transplant. 2020; 56(2):376-386. PMC: 7870804. DOI: 10.1038/s41409-020-01027-6. View

Steffin D, Muhsen I, Hill L, Ramos C, Ahmed N, Hegde M . Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IECs. Blood. 2022; 140(1):16-24. PMC: 9346960. DOI: 10.1182/blood.2022015728. View

Socie G, Salooja N, Cohen A, Rovelli A, Carreras E, Locasciulli A . Nonmalignant late effects after allogeneic stem cell transplantation. Blood. 2003; 101(9):3373-85. DOI: 10.1182/blood-2002-07-2231. View

Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L . CAR-HEMATOTOX: a model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021; 138(24):2499-2513. PMC: 8893508. DOI: 10.1182/blood.2020010543. View

Cheung Y, Brinkman T, Mulrooney D, Mzayek Y, Liu W, Banerjee P . Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long-term survivors of childhood acute lymphoblastic leukemia. Cancer. 2017; 123(17):3410-3419. PMC: 5570612. DOI: 10.1002/cncr.30742. View

Juluri K, Wu Q, Voutsinas J, Hou J, Hirayama A, Mullane E . Severe cytokine release syndrome is associated with hematologic toxicity following CD19 CAR T-cell therapy. Blood Adv. 2021; 6(7):2055-2068. PMC: 9006285. DOI: 10.1182/bloodadvances.2020004142. View

10.

Qayed M, Bleakley M, Shah N . Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia. Curr Opin Hematol. 2021; 28(6):373-379. PMC: 9079121. DOI: 10.1097/MOH.0000000000000685. View

11.

Holland E, Yates B, Ling A, Yuan C, Wang H, Stetler-Stevenson M . Characterization of extramedullary disease in B-ALL and response to CAR T-cell therapy. Blood Adv. 2021; 6(7):2167-2182. PMC: 9006258. DOI: 10.1182/bloodadvances.2021006035. View

12.

Laetsch T, Maude S, Rives S, Hiramatsu H, Bittencourt H, Bader P . Three-Year Update of Tisagenlecleucel in Pediatric and Young Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia in the ELIANA Trial. J Clin Oncol. 2022; 41(9):1664-1669. PMC: 10022844. DOI: 10.1200/JCO.22.00642. View

13.

Mulder R, Font-Gonzalez A, Green D, Loeffen E, Hudson M, Loonen J . Fertility preservation for male patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 2021; 22(2):e57-e67. DOI: 10.1016/S1470-2045(20)30582-9. View

14.

Cheung Y, Sabin N, Reddick W, Bhojwani D, Liu W, Brinkman T . Leukoencephalopathy and long-term neurobehavioural, neurocognitive, and brain imaging outcomes in survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy: a longitudinal analysis. Lancet Haematol. 2016; 3(10):e456-e466. PMC: 5417340. DOI: 10.1016/S2352-3026(16)30110-7. View

15.

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

16.

Holland E, Molina J, Dede K, Moyer D, Zhou T, Yuan C . Efficacy of second CAR-T (CART2) infusion limited by poor CART expansion and antigen modulation. J Immunother Cancer. 2022; 10(5). PMC: 9086629. DOI: 10.1136/jitc-2021-004483. View

17.

Hines M, Knight T, McNerney K, Leick M, Jain T, Ahmed S . Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome. Transplant Cell Ther. 2023; 29(7):438.e1-438.e16. PMC: 10330221. DOI: 10.1016/j.jtct.2023.03.006. View

18.

Pfitzer C, Orawa H, Balcerek M, Langer T, Dirksen U, Keslova P . Dynamics of fertility impairment and recovery after allogeneic haematopoietic stem cell transplantation in childhood and adolescence: results from a longitudinal study. J Cancer Res Clin Oncol. 2014; 141(1):135-42. DOI: 10.1007/s00432-014-1781-5. View

19.

Bhatia S, Armenian S, Landier W . How I monitor long-term and late effects after blood or marrow transplantation. Blood. 2017; 130(11):1302-1314. DOI: 10.1182/blood-2017-03-725671. View

20.

Rejeski K, Greco R, Onida F, Sanchez-Ortega I, Bonini C, Sureda A . An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA. Hemasphere. 2023; 7(5):e889. PMC: 10145722. DOI: 10.1097/HS9.0000000000000889. View