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CAR-T treatment is safe and effective in adult patients with Down syndrome and B-cell acute lymphoblastic leukemia (B-ALL)

Bone Marrow Transplantation (2024)Cite this article

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Treatment with chimeric antigen receptor T-cell (CAR-T) therapy targeting leukemic surface antigens, such as CD19 or CD22, is assuming a prominent role in the management of B-cell acute lymphoblastic leukemia (B-ALL). In pediatric and adult populations, tisagenlecleucel (tisa-cel) and brexucabtagene autoleucel (brexu-cel) can achieve overall response rates of 82% and 71%, respectively [1, 2]. Three-year PFS of tisa-cel is 44%, and median relapse-free survival was 11.6 months for brexu-cel.

The role of consolidation therapy with allogeneic stem cell transplant (allo-SCT) for all patients treated with CAR-T for B-ALL remains uncertain, lacking direct trials addressing this specific issue [3].

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References

  1. Laetsch TW, Maude SL, Rives S, Hiramatsu H, Bittencourt H, Bader P, et al. Three-year update of tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial. J Clin Oncol. 2023;41:1664–9.

    Article  CAS  PubMed  Google Scholar 

  2. Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD et al. Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. J Hematol Oncol. 2022; 15. https://doi.org/10.1186/S13045-022-01379-0.

  3. Pasvolsky O, Kebriaei P, Shah BD, Jabbour E, Jain N. Chimeric antigen receptor T-cell therapy for adult B-cell acute lymphoblastic leukemia: state-of-the-(C)ART and the road ahead. Blood Adv. 2023;7:3350–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial. Nat Med. 2023;29:2593–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sehgal A, Hoda D, Riedell PA, Ghosh N, Hamadani M, Hildebrandt GC, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066–77.

    Article  CAS  PubMed  Google Scholar 

  6. Hasle H, Friedman JM, Olsen JH, Rasmussen SA. Low risk of solid tumors in persons with Down syndrome. Genet Med. 2016;18:1151–7.

    Article  PubMed  Google Scholar 

  7. Baruchel A, Bourquin JP, Crispino J, Cuartero S, Hasle H, Hitzler J, et al. Down syndrome and leukemia: from basic mechanisms to clinical advances. Haematologica. 2023;108:2570–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li Z, Chang TC, Junco JJ, Devidas M, Li Y, Yang W, et al. Genomic landscape of Down syndrome-associated acute lymphoblastic leukemia. Blood. 2023;142:172–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Buitenkamp TD, Izraeli S, Zimmermann M, Forestier E, Heerema NA, Van Den Heuvel-Eibrink MM, et al. Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group. Blood. 2014;123:70–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Barwe SP, Kolb EA, Gopalakrishnapillai A. Down syndrome and leukemia: an insight into the disease biology and current treatment options. Blood Rev. 2024;64:101154.

    Article  CAS  PubMed  Google Scholar 

  11. Rubin CM, Mick R, Johnson FL. Bone marrow transplantation for the treatment of haematological disorders in Down’s syndrome: toxicity and outcome. Bone Marrow Transpl. 1996;18:533–40.

    CAS  Google Scholar 

  12. Hitzler JK, He W, Doyle J, Cairo M, Camitta BM, Chan KW, et al. Outcome of transplantation for acute lymphoblastic leukemia in children with Down syndrome. Pediatr Blood Cancer. 2014;61:1126–8.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sora F, Annunziata M, Laurenti L, Giammarco S, Chiusolo P, Innocenti I et al. Blinatumomab as a successful and safe therapy in Down syndrome patients with relapsed/refractory b-precursor acute lymphoblastic leukaemia: case reports and literature review. Pediatr Blood Cancer. 2021; 68. https://doi.org/10.1002/PBC.29044.

  14. Shah NN, Lee DW, Yates B, Yuan CM, Shalabi H, Martin S, et al. Long-term follow-up of CD19-CAR t-cell therapy in children and young adults with B-ALL. J Clin Oncol. 2021;39:1650–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hiramatsu H, Adachi S, Umeda K, Kato I, Eldjerou L, Agostinho AC, et al. Efficacy and safety of tisagenlecleucel in Japanese pediatric and young adult patients with relapsed/refractory B cell acute lymphoblastic leukemia. Int J Hematol. 2020;111:303–10.

    Article  CAS  PubMed  Google Scholar 

  16. Traube C, Silver G, Kearney J, Patel A, Atkinson TM, Yoon MJ, et al. Cornell assessment of pediatric delirium: a valid, rapid, observational tool for screening delirium in the PICU. Crit Care Med. 2014;42:656–63.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transpl. 2019;25:625–38.

    Article  CAS  Google Scholar 

  18. Wright LK, Stallings EB, Cragan JD, Pabst LJ, Alverson CJ, Oster ME. Narrowing the survival gap: trends in survival of individuals with down syndrome with and without congenital heart defects born 1979 to 2018. J Pediatr. 2023; 260. https://doi.org/10.1016/J.JPEDS.2023.113523.

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Acknowledgements

This research received the support of “Centro di Ricerca sulle cellule staminali emopoietiche e le terapie cellulari” “Università Cattolica del Sacro Cuore, Roma”.

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Authors and Affiliations

  1. Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze di Laboratorio ed Ematologiche, Rome (IT), Italy

    Eugenio Galli, Patrizia Chiusolo, Simona Sica & Federica Sorà

  2. Università Cattolica del Sacro Cuore, Sezione di Ematologia, Dipartimento di Scienze Radiologiche ed Ematologiche, Rome (IT), Italy

    Alessandro Corrente, Patrizia Chiusolo, Simona Sica & Federica Sorà

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  1. Eugenio Galli
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  2. Alessandro Corrente
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  5. Federica Sorà
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Contributions

EG and FS designed the study. EG, PC, and AC collected clinical data and revised the literature. EG, PC, FS, and SS clinically managed patients. All authors critically revised and approved the paper.

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Correspondence to Simona Sica.

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EG, SS and FS received grants from Kite Gilead. The authors declare no other competing conflicts of interest.

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Galli, E., Corrente, A., Chiusolo, P. et al. CAR-T treatment is safe and effective in adult patients with Down syndrome and B-cell acute lymphoblastic leukemia (B-ALL). Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02386-0

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  • DOI: https://doi.org/10.1038/s41409-024-02386-0

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