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Comparison of short- and long-term adverse kidney outcomes after chimeric antigen receptor T cell therapy and autologous hematopoietic stem cell transplant for diffuse large B cell lymphoma

Bone Marrow Transplantation volume 57, pages 1623–1625 (2022)Cite this article

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Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B cells that can arise from a variety of tissues [1]. While first-line chemotherapy can induce remission in ~60% of patients [2], cellular therapies have demonstrated robust activity in relapsed and refractory disease. The standard of care for chemo-sensitive DLBCL are autologous hematopoietic cell transplantation (auto-HSCT) and allogeneic hematopoietic cell transplantation. Recently, however, chimeric antigen receptor T cell (CAR-T) has been approved for first relapse of high-risk patients and relapsed or refractory disease—inducing a durable remission in a subset of patients with DLBCL that were previously unresponsive to treatment [3, 4]. Despite its success, CAR-T therapy has significant acute toxicities, including cytokine release syndrome (CRS) and neurotoxicity, which can be fatal [5].

Acute kidney injury (AKI) is a common complication after CAR-T or HSCT [6,7,8]. Despite the rapid increase in use of CAR-T therapy and its association with AKI, the long-term kidney risks in cancer survivors exposed to this therapy are largely unknown. We sought to compare the incidence and risk factors for AKI and chronic kidney function decline in patients with DLBCL treated with CAR-T vs. auto-HSCT.

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Fig. 1: Acute kidney injury, chronic kidney function decline and the mean percent reduction in estimated glomerular filtration rate among patients after autologous hematopoietic stem cell transplant or chimeric antigen receptor T cell therapy.

Data availability

The data that support the findings of this study are available from the Research Patient Data Registry at Mass General Brigham, but restrictions apply as they were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission from Mass General Brigham.

References

  1. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90. https://doi.org/10.1182/blood-2016-01-643569.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bal S, Costa LJ, Sauter C, Litovich C, Hamadani M. Outcomes of autologous hematopoietic cell transplantation in diffuse large B cell lymphoma refractory to firstline chemoimmunotherapy. Transpl Cell Ther. 2021;27:55 e51–55 e57. https://doi.org/10.1016/j.bbmt.2020.09.004.

    Article  CAS  Google Scholar 

  3. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17. https://doi.org/10.1056/NEJMoa1407222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377:2545–54. https://doi.org/10.1056/NEJMoa1708566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Primary analysis of Juliet: a global, pivotal, phase 2 trial of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma. Blood. 2017;130:577. https://doi.org/10.1182/blood.V130.Suppl_1.577.577.

    Article  Google Scholar 

  6. Gupta S, Seethapathy H, Strohbehn IA, Frigault MJ, O’Donnell EK, Jacobson CA, et al. Acute kidney injury and electrolyte abnormalities after chimeric antigen receptor T-cell (CAR-T) therapy for diffuse large B-cell lymphoma. Am J Kidney Dis. 2020;76:63–71. https://doi.org/10.1053/j.ajkd.2019.10.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gutgarts V, Jain T, Zheng J, Maloy MA, Ruiz JD, Pennisi M, et al. Acute kidney injury after CAR-T cell therapy: low incidence and rapid recovery. Biol Blood Marrow Transplant. 2020;26:1071–6. https://doi.org/10.1016/j.bbmt.2020.02.012.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hingorani S. Renal complications of hematopoietic-cell transplantation. N Engl J Med. 2016;374:2256–67. https://doi.org/10.1056/NEJMra1404711.

    Article  PubMed  Google Scholar 

  9. 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. https://doi.org/10.1016/j.bbmt.2018.12.758.

    Article  CAS  Google Scholar 

  10. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pr. 2012;120:c179–84. https://doi.org/10.1159/000339789.

    Article  Google Scholar 

  11. Ansari R, Caimi P, Zhengyi C, Rashidi A. Renal outcomes after chimeric antigen receptor T-cell (CAR-T) therapy: a single center perspective. Nephrol Dial Transpl. 2022. https://doi.org/10.1093/ndt/gfac048.

    Article  Google Scholar 

  12. Ellis MJ, Parikh CR, Inrig JK, Kanbay M, Patel UD. Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transpl. 2008;8:2378–90. https://doi.org/10.1111/j.1600-6143.2008.02408.x.

    Article  CAS  Google Scholar 

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Acknowledgements

This cohort includes 114 patients that were previously reported in studies of AKI after CAR-T (PMID: 33098925, 31973908).

Funding

MES is supported by the National Institutes of Health award R01 DK130839, K23DK117014, and the Claflin Distinguished Scholars award. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. These organizations were not involved in study design, analysis, interpretation, or manuscript creation.

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Authors and Affiliations

  1. Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA

    Paul Hanna, Ian Strohbehn, Daiana Moreno, Destiny Harden, Harish Seethapathy, Meghan Lee, Tianqi Ouyang & Meghan E. Sise

  2. Department of Medicine, Division of Nephrology, Brigham and Women’s Hospital, Boston, MA, USA

    Shruti Gupta

  3. Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, MA, USA

    Shruti Gupta

  4. Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA

    Matthew Frigault

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Contributions

Research idea and study design: MES, MF, and PH; data acquisition: PH, DM, DH, ML, and IS; data analysis/interpretation: PH, IS, MF, SG, HS, and MES; statistical analysis: PH, TO, and MES; supervision or mentorship: MF and MES. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s contributions, and agrees to ensure that questions about the accuracy or integrity of any portion of the work are appropriately investigated and resolved, including with documentation in the literature if appropriate.

Corresponding author

Correspondence to Meghan E. Sise.

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Competing interests

PH, IS, DM, DH, HS, ML, TO, and MES have nothing to declare. MF is a consultant for Novartis, Kite/Gilead, BMS, Iovance, JnJ/Legend, and Arcellx. SG receives research funding from BTG International, GE Healthcare and NIH NIDDK K23DKDK125672.

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Supplementary information

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Supplemental Figure 1. Patient flow

41409_2022_1767_MOESM3_ESM.png

Supplemental Figure 2. Comparison of acute kidney injury rates at 15, 30, and 90 days among patients receiving autologous hematopoietic stem cell transplant or chimeric antigen receptor T cell therapy

Supplemental Table 1. Baseline characteristics of the overall cohort and the subset followed for at least 12 months

41409_2022_1767_MOESM5_ESM.xlsx

Supplemental Table 2. Predictors of AKI among patients receiving autologous hematopoietic stem cell transplant or chimeric antigen receptor T cell therapy

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Supplemental Table 3. Predictors of chronic kidney function decline among patients receiving autologous hematopoietic stem cell transplant or chimeric antigen receptor T cell therapy

41409_2022_1767_MOESM7_ESM.xlsx

Supplemental Table 4: Predictors of acute kidney injury among patients receiving chimeric antigen receptor T cell therapy

41409_2022_1767_MOESM8_ESM.xlsx

Supplemental Table 5. Predictors of chronic kidney function decline among patients receiving chimeric antigen receptor T cell therapy who survived a year.

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Hanna, P., Strohbehn, I., Moreno, D. et al. Comparison of short- and long-term adverse kidney outcomes after chimeric antigen receptor T cell therapy and autologous hematopoietic stem cell transplant for diffuse large B cell lymphoma. Bone Marrow Transplant 57, 1623–1625 (2022). https://doi.org/10.1038/s41409-022-01767-7

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