|LETTER TO THE EDITOR
|Ahead of print
Testing for latent tuberculosis before starting patients on immune checkpoint inhibitors
Department of Medicine and Cellular and Molecular Medicine, University of California, San Diego, U.S.A.
|Date of Submission||03-Apr-2020|
|Date of Decision||30-Apr-2020|
|Date of Acceptance||09-Jun-2020|
|Date of Web Publication||21-Jun-2021|
Departments of Medicine and Cellular and Molecular Medicine, University of California, San Diego
Source of Support: None, Conflict of Interest: None
Multiple case reports have been published on the risk of tuberculosis activation in patients on immune checkpoint inhibitors (ICPIs) and have come to my attention. To this matter, I caution clinicians to test for latent tuberculosis (LTB) before starting their patients on ICPIs.
The 2018 Nobel Prize in Medicine and Physiology was awarded to Tasuku Honjo and James Allison for their discovery of ICPIs, a revolutionary new cancer therapy. An important yet often overlooked phenomena when using ICPIs though is the risk of infection reactivation due to immunosuppression. Activation of asymptomatic and undiagnosed LTB is a significant concern as demonstrated by multiple case studies.,,,,,, One possible mechanism for reactivation of tuberculosis (TB) in patients on anti-PD-1 therapy is pictorially depicted in [Figure 1]. Briefly, PD-1 expressing T-cells bind to PD-L1 on cells infected with Mycobacterium tuberculosis. These cells remain quiescent until anti-PD-1 therapy for an unrelated malignancy is started. This blocking of the immune handshake may reactivate LTB leading to pulmonary/disseminated TB.
|Figure 1: Pictorial depiction of one possible mechanism for tuberculosis (TB) activation by anti-PD-1 immunotherapy. Yellow rods indicate Mycobacterium tuberculosis (Mtb). Image created with objects sourced from Servier Medical Art (http://smart.servier.com/), licensed under a Creative Common Attribution 3.0 Generic License.|
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In light of all these studies, it is imperative that physicians test for LTB before starting patients on ICPIs. This caution is especially targeted to physicians practicing in countries where TB is endemic. The established way to test for asymptomatic LTB is by interferon-γ release assays such as the QuantiFERON-TB Gold test (high-specificity of >99%) as was used in a recent study. Newer methods such as host gene expression profiles and differences in cellular phenotypes are also being studied as possible ways to diagnose LTB.
If a diagnosis of LTB is established, further therapeutic decisions should be taken in consultation with a pulmonologist/TB specialist. A 4-week isoniazid chemoprophylaxis is one possible method to treat LTB and has been successful in preventing TB reactivation in patients on anti-TNF therapy. Finally, the potential risk to benefit ratio of ICPIs should also be taken into consideration on a case-by-case basis in patients with untreated LTB. Longer follow-ups of patients on ICPIs and pre-clinical model studies are likely to throw further light on these matters.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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