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Active and latent tuberculosis infections in patients treated with immune checkpoint inhibitors in a non-endemic tuberculosis area

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Abstract

Background

Immune checkpoint inhibitors (ICIs) blocking inhibitory immune pathways (e.g., programmed cell death protein-1/-ligand1 [PD-1/PD-L1]) have revolutionized cancer therapy for numerous malignancies. There have been an increasing number of cases of active tuberculosis (TB) reported in association with ICI use, and recent data suggest alterations in immune responses in TB by ICI. The aim of this study was to characterize the frequency of latent tuberculosis infection (LTBI) and active TB in a large cohort of ICI-treated patients in a low TB incidence area.

Methods

We conducted a retrospective review of all ICI-treated patients tested for TB between January, 1997 and August, 2018. Data extracted included patient demographics, TB risk factors, latent/active TB diagnosis and treatment, tumor type, ICI used, immunosuppressive medications, and mortality related to TB.

Results

We identified 1844 ICI-treated patients, including 30 abnormal TB test results. Two patients were diagnosed with active TB, both prior to starting ICI therapy. One patient was treated for TB prior to starting ICI and the other patient was successfully treated concurrently. Seven patients were diagnosed with LTBI and none developed active TB. Twenty patients had indeterminate interferon gamma release assays (IGRA).

Conclusion

Despite recent reports of TB in patients taking ICI, we found no patients developing TB during ICI therapy in our large retrospective cohort of ICI-treated cancer patients in a non-endemic TB area. The high rate of indeterminate IGRA results suggests the need for prospective research with better diagnostics to quantify the actual risk of TB in this patient population.

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Abbreviations

TB:

Active tuberculosis

iAE:

Immune-related adverse event

ICI:

Immune checkpoint inhibitor

IGRA:

Interferon gamma release assay

LTBI:

Latent tuberculosis infection

Mtb:

Mycobacterium tuberculosis

PD-1:

Programmed cell death protein-1

PD-L1:

Programmed death ligand 1

TST:

Tuberculin skin test

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Acknowledgements

Heidi Finnes, PharmD, RPh and Lisa Kottschade, APRN, CNP assisted in identifying patients treated with ICI at Mayo Clinic.

Funding

The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905, USA

    Gregory R. Stroh, Tobias Peikert & Patricio Escalante

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  1. Gregory R. Stroh
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  2. Tobias Peikert
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  3. Patricio Escalante
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Corresponding author

Correspondence to Patricio Escalante.

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Conflict of interest

GRS has no relevant financial or non-financial interests to disclose. TP participated in Advisory Boards for AstraZeneca and Novocure, outside the scope of the submitted work. All fees were paid to Mayo Clinic. PE participated in a short-term advisory scientific board for DiaSorin Molecular, which was outside the scope of the submitted work. Honorarium was paid to Mayo Clinic. PE has also filed two patent applications related to immunodiagnostic laboratory methodologies for latent tuberculosis infection for intellectual property protection purposes. To date, there has been no income or royalties associated with those filed patent applications. Otherwise, PE does not have other conflicts of interest COI to disclose. This paper’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or Mayo Clinic. No other financial or material support for this work was provided to the authors.

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Stroh, G., Peikert, T. & Escalante, P. Active and latent tuberculosis infections in patients treated with immune checkpoint inhibitors in a non-endemic tuberculosis area. Cancer Immunol Immunother 70, 3105–3111 (2021). https://doi.org/10.1007/s00262-021-02905-8

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  • DOI: https://doi.org/10.1007/s00262-021-02905-8

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