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:

Chimeric antigen receptor T-cell therapy for HIV-associated diffuse large B-cell lymphoma: case report and management recommendations

Bone Marrow Transplantation volume 56, pages 679–682 (2021)Cite this article

Subjects

Human immunodeficiency virus-positive (HIV+) patients are at substantially higher risk of hematologic malignancies, including an 18-fold increased risk of diffuse large B-cell lymphoma (DLBCL) [1]. While antiretroviral therapy (ART) regimens have significantly improved viral control and reduced the risk of malignancy, HIV+ patients continue to be at increased risk irrespective of CD4 count and viral load [1]. The therapeutic goal for HIV+ patients with DLBCL is curative, but patients who are refractory to chemotherapy or relapse post autologous transplant (auto-HCT) have poor outcomes. Recently, CD19-targeting chimeric antigen receptor T (CAR-T) therapies became available for patients with relapsed/refractory (R/R) DLBCL and demonstrated overall response rates of 50–85% and complete response rates of 40–52% [2, 3]. However, HIV+ patients have been excluded from all registration CAR-T-cell clinical trials, leaving uncertainty regarding safety and efficacy of CAR-T therapies in HIV-infected individuals. We report here our experience treating a well-controlled HIV+ male with aggressive multiply relapsed DLBCL with axicabtagene ciloleucel and discuss steps to optimize success of CAR-T therapy and management of concomitant HIV and R/R DLBCL.

A 49-year-old male with well-controlled HIV on ART since 2008, without AIDS-defining illness, presented with a 3-week history of progressive nasal obstruction. MRI identified a locally destructive right nasal cavity mass and subsequent excisional biopsy demonstrated HIV-related DLBCL with high-grade features, nongerminal center subtype, with expression of CD19, partial CD20, BLC2, and MYC in >40% of cells. Ki-67 was 90%. c-MYC was not rearranged. PET/CT confirmed hypermetabolic nasal cavity mass and cervical adenopathy without distant disease. He was diagnosed with stage II-E HIV-related DLBCL, IPI 0. Quantitative serum HIV was undetectable and CD4 count was 378 cells/µL. The patient achieved CR after induction therapy with dose adjusted R-EPOCH and was consolidated with autologous hematopoietic cell transplantation. On day +100 post transplant, the patient experienced excessive right eye watering and biopsy of the lacrimal gland confirmed relapsed high-grade DLBCL similar to prior histology. His disease was managed with localized radiotherapy and lenalidomide followed by ibrutinib for more than 1 year before he experienced widespread relapse.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Clinical course timeline.

References

  1. Gibson TM, Morton LM, Shiels MS, Clarke CA, Engels EA. Risk of non-Hodgkin lymphoma subtypes in HIV-infected people during the HAART era: a population-based study. AIDS. 2014;28:2313–8.

    Article  CAS  Google Scholar 

  2. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531–44.

    Article  CAS  Google Scholar 

  3. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45–56.

    Article  CAS  Google Scholar 

  4. Abramson JS, Irwin KE, Frigault MJ, Dietrich J, McGree B, Jordan JT, et al. Successful anti-CD19 CAR T-cell therapy in HIV-infected patients with refractory high-grade B-cell lymphoma. Cancer. 2019;125:3692–8.

    Article  Google Scholar 

  5. Abbasi A, Peeke S, Shah N, Mustafa J, Khatun F, Lombardo A, et al. Axicabtagene ciloleucel CD19 CAR-T cell therapy results in high rates of systemic and neurologic remissions in ten patients with refractory large B cell lymphoma including two with HIV and viral hepatitis. J Hematol Oncol. 2020;13:1.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by T32 HL007062.

Author information

Authors and Affiliations

  1. Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Jeremy Allred, Fiona He, Murali Janakiram, Joseph Maakaron, Claire Carrier & Veronika Bachanova

  2. University of Minnesota Medical school, Minneapolis, MN, USA

    Kharmen Bharucha

  3. Department of Radiology, University of Minnesota, Minneapolis, MN, USA

    Can Özütemiz

  4. Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA

    Bartosz Grzywacz

Authors
  1. Jeremy Allred
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kharmen Bharucha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Can Özütemiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fiona He
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Murali Janakiram
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joseph Maakaron
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Claire Carrier
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bartosz Grzywacz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Veronika Bachanova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Veronika Bachanova.

Ethics declarations

Conflict of interest

VB recieved research funding from Novartis, Gamida Cell, Incyte and is an advisory board member for Kite, UNUM, Karyapharma. All others authors declare no conflict of interest.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Allred, J., Bharucha, K., Özütemiz, C. et al. Chimeric antigen receptor T-cell therapy for HIV-associated diffuse large B-cell lymphoma: case report and management recommendations. Bone Marrow Transplant 56, 679–682 (2021). https://doi.org/10.1038/s41409-020-01018-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-020-01018-7

This article is cited by

Search

Advanced search

Quick links