Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Progressive multifocal leukoencephalopathy after CAR-T cell therapy

Bone Marrow Transplantation volume 59, pages 1780–1782 (2024)Cite this article

Subjects

Access through your institution
Buy or subscribe

Progressive multifocal leukoencephalopathy (PML) is a rare and devastating viral infection that affects the central nervous system (CNS) of severely immunocompromised patients. Lymphodepletion followed by chimeric antigen receptor T cell (CAR-T) therapy to treat certain hematologic malignancies can result in prolonged immunocompromised status. The recipients of CAR-T therapy are at risk of opportunistic infections including progressive multifocal leukoencephalopathy (PML). CAR-T therapy itself is associated with early and late neurotoxicities and can make the diagnosis of PML difficult [1]. Given its high mortality rate (30–50%) in the first few months following initial diagnosis, early rapid diagnosis is important to prevent permanent neurological damage [2]. Here, we discuss a case of PML in a patient with relapsed diffuse large B cell lymphoma (DLBCL) two years after the CD19 CAR-T therapy. We have also provided a table summary of four other published cases of PML after CAR-T therapy and reviewed relevant literature on the management.

A 73-year-old female with DLBCL, refractory to R-CHOP and lenalidomide and Revlimid was referred for CD19-directed CAR-T therapy. She received fludarabine and cyclophosphamide (Flu/Cy) lymphodepletion followed by axicabtagene ciloleucel (axi-cel, CD19-directed CAR-T therapy) on the ZUMA-1 clinical trial (NCT02348216). Early complications included grade 2 cytokine release syndrome (CRS) and grade 2 immune effector cell neurotoxicity syndrome (ICANS). She received tocilizumab and dexamethasone, with a resolution of these side effects. Subsequent PET/CT scan showed complete remission. She developed persistent hypogammaglobulinemia following CAR-T and was treated with intravenous immunoglobulin (IVIG). She also developed COVID-19 infection twice (6 months and 9 months) after axi-cel, for which she was treated with hydroxychloroquine and convalescent plasma.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Hartmann J, Schüßler‐Lenz M, Bondanza A, Buchholz CJ. Clinical development of CAR-T cells—challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med. 2017;9:1183–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Pavlovic D, Patera AC, Nyberg F, Gerber M, Liu M, for the Progressive Multifocal Leukoencephalopathy Consortium. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives. Ther Adv Neurol Disord. 2015;8:255–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Mackenzie S, Shafat M, Roddy H, Hyare H, Neill L, Marzolini MAV, et al. Pembrolizumab for the treatment of progressive multifocal leukoencephalopathy following anti‐CD19 CAR‐T therapy: a case report. eJHaem. 2021;2:848–53.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis Rheum. 2012;64:3043–51.

    Article  CAS  PubMed  Google Scholar 

  5. Felli V, Di Sibio A, Anselmi M, Gennarelli A, Sucapane P, Splendiani A, et al. Progressive multifocal leukoencephalopathy following treatment with rituximab in an HIV-negative patient with non-Hodgkin lymphoma: a case report and literature review. Neuroradiol J. 2014;27:657–64.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Goldman A, Raschi E, Chapman J, Santomasso BD, Pasquini MC, Perales MA, et al. Progressive multifocal leukoencephalopathy in patients treated with chimeric antigen receptor T cells. Blood. 2023;141:673–7.

    Article  CAS  PubMed  Google Scholar 

  7. Mateen FJ, Muralidharan R, Carone M, Van De Beek D, Harrison DM, Aksamit AJ, et al. Progressive multifocal leukoencephalopathy in transplant recipients. Ann Neurol. 2011;70:305–22.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Sdrimas K, Diaz-Paez M, Camargo JF, Lekakis LJ. Progressive multifocal leukoencephalopathy after CAR-T therapy. Int J Hematol. 2020;112:118–21.

    Article  CAS  PubMed  Google Scholar 

  9. Ahrendsen JT, Sehgal K, Sarangi S, Uhlmann EJ, Varma H, Arnason J, et al. Progressive multifocal leukoencephalopathy after chimeric antigen receptor T-cell therapy for recurrent non-Hodgkin lymphoma. J Hematol. 2021;10:212–6.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dunham SR, Schmidt R, Clifford DB. Treatment of progressive multifocal leukoencephalopathy using immune restoration. Neurotherapeutics. 2020;17:955–65.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Walter O, Treiner E, Bonneville F, Mengelle C, Vergez F, Lerebours F, et al. Treatment of progressive multifocal leukoencephalopathy with nivolumab. N Engl J Med. 2019;380:1674–6.

    Article  PubMed  Google Scholar 

  12. Holmes A, Wellings T, Walsh O, Rowlings P. Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab. J Neurovirol. 2020;26:961–3.

    Article  CAS  PubMed  Google Scholar 

  13. Muftuoglu M, Olson A, Marin D, Ahmed S, Mulanovich V, Tummala S, et al. Allogeneic BK virus–specific T cells for progressive multifocal leukoencephalopathy. N Engl J Med. 2018;379:1443–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mian A, Andrapalliyal N, Weathers AL, Pohlman B, Hill BT. Late occurrence of progressive multifocal leukoencephalopathy after anti-CD19 chimeric antigen receptor T-cell therapy. Eur J Haematol. 2021;106:584–8. https://doi.org/10.1111/ejh.13583.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Trials Office, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

    Michael Montoya

  2. Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    Hannah J. Harmsen

  3. Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Brittney Baer, Nancy Long, Amy Messimore, Reena V. Jayani, Adetola Kassim, Andrew P. Jallouk, James Jerkins, Eden A. Biltibo, Bipin N. Savani, Bhagirathbhai Dholaria, Olalekan Oluwole & David S. Morgan

Authors
  1. Michael Montoya
    View author publications

    Search author on:PubMed Google Scholar

  2. Hannah J. Harmsen
    View author publications

    Search author on:PubMed Google Scholar

  3. Brittney Baer
    View author publications

    Search author on:PubMed Google Scholar

  4. Nancy Long
    View author publications

    Search author on:PubMed Google Scholar

  5. Amy Messimore
    View author publications

    Search author on:PubMed Google Scholar

  6. Reena V. Jayani
    View author publications

    Search author on:PubMed Google Scholar

  7. Adetola Kassim
    View author publications

    Search author on:PubMed Google Scholar

  8. Andrew P. Jallouk
    View author publications

    Search author on:PubMed Google Scholar

  9. James Jerkins
    View author publications

    Search author on:PubMed Google Scholar

  10. Eden A. Biltibo
    View author publications

    Search author on:PubMed Google Scholar

  11. Bipin N. Savani
    View author publications

    Search author on:PubMed Google Scholar

  12. Bhagirathbhai Dholaria
    View author publications

    Search author on:PubMed Google Scholar

  13. Olalekan Oluwole
    View author publications

    Search author on:PubMed Google Scholar

  14. David S. Morgan
    View author publications

    Search author on:PubMed Google Scholar

Contributions

MM and BD designed the study and wrote the manuscript. HH, BB, NL, AM, RJ, AK, AJ, JJ, EB, BS, OO, and DM reviewed and provided edits to the submitted manuscript. All authors gave final approval for the manuscript.

Corresponding author

Correspondence to Bhagirathbhai Dholaria.

Ethics declarations

Competing interests

BD reports research funding from Gilead/Kite, BMS, Wugen, Adicet, and Poseida. consultant: Gilead/Kite, Janssen.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Montoya, M., Harmsen, H.J., Baer, B. et al. Progressive multifocal leukoencephalopathy after CAR-T cell therapy. Bone Marrow Transplant 59, 1780–1782 (2024). https://doi.org/10.1038/s41409-024-02410-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-024-02410-3

Search

Advanced search

Quick links