Anti-PD1 Antibody Treatment and the Development of Acute Pulmonary Tuberculosis

Fujita, Kohei; Terashima, Takaya; Mio, Tadashi

doi:10.1016/j.jtho.2016.07.006

Cited by 127 publications

(100 citation statements)

References 10 publications

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“…This is likely due to excessive inflammation and increased focal necrosis. 121 Trials on the use of checkpoint inhibitors which block the PD1/PD-L1 pathway as adjunt to TB therapy are being considered.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

287

260

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

287

260

View full text Add to dashboard Cite

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“…To our knowledge, there have only been seven reports about acute Tbc infections or reactivations in patients receiving ICI treatment . In this study, Three patients were newly diagnosed with pulmonary Tbc during their anti‐PD‐1 treatment.…”

Section: Discussionmentioning

confidence: 91%

“…Tuberculosis is still a burdensome disease worldwide. With regard to pulmonary tuberculosis, only seven patients treated with ICIs have been described in previous reports, and the association of ICIs with Tbc reactivation remains ambiguous …”

Section: Introductionmentioning

confidence: 99%

“…With regard to pulmonary tuberculosis, only seven patients treated with ICIs have been described in previous reports, and the association of ICIs with Tbc reactivation remains ambiguous. [11][12][13][14][15][16][17] At present, over 10 million people in the United States have an autoimmune disease. 18 According to a Medicare database analysis, approximately 13.5-24.6% of lung cancer patients in the United States have an autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

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PD‐1 inhibitors for non‐small cell lung cancer patients with special issues: Real‐world evidence

et al. 2020

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Background Immune checkpoint inhibitors (ICIs) have provided new therapeutic options for non‐small cell lung cancer(NSCLC) patients. However, due to concerning increases in immune‐related adverse events, clinical trials usually exclude patients with special issues such as viral hepatitis, tuberculosis (Tbc), interstitial lung disease (ILD) and autoimmune disease. Methods We retrospectively reviewed the medical records of NSCLC patients who received ICIs, and analyzed the clinical outcomes of patients with special issues. Results Between January 2015 and October 2018, 237 patients received ICIs. Of these patients, 26% (61/237) had special issues: 32 had hepatitis B viral (HBV) infections, 20 Tbc, six ILD, one HIV infection, one Behçet's disease and a past HBV infection, and one rheumatoid arthritis. The incidence of hepatitis tended to be higher in patients with HBV infections than in those without (18.8% vs 8.91%, P = .082). Severe hepatitis (grade 3 or higher) was more common in HBV‐infected patients (12.5% vs 1.9%, P = .0021), but the AEs were well‐managed. During ICI treatment, three of the 20 patients with a history of pulmonary Tbc developed active pulmonary Tbc, considered reactivations. No aggravation of ILD was noted. One RA patient experienced a disease flare and was treated with a low‐dose steroid. There was no significant difference in the overall response rate or progression‐free survival between patients with and without special issues. Conclusion Given the relatively low incidence of immune‐related AEs and the comparability of clinical outcomes, ICIs can be treatment option of NSCLC patients with special issues.

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“…Two remarkable cases that suggested reactivation of the immune response to microorganisms by the treatment with nivolumab have been reported. These reports suggested that immune checkpoint inhibitors have an immunomodulatory effect that enhances the immune reaction to infectious disease and often causes the reactivation of latent infections . We experienced acute progression of pulmonary aspergillosis in a patient with lung cancer receiving nivolumab treatment.…”

Section: Introductionmentioning

confidence: 95%

Acute progression of aspergillosis in a patient with lung cancer receiving nivolumab

Uchida

Fujita

Nakatani

et al. 2017

Respirology Case Reports

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A 65‐year‐old man with chronic progressive pulmonary aspergillosis (CPPA) was admitted for the treatment of lung adenocarcinoma while receiving an immune checkpoint inhibitor, nivolumab. The tumour responded well to the therapy, but the cavity of CPPA became large in contrast to the tumour after 20 courses of therapy. He was diagnosed as having exacerbation of CPPA and successfully and concurrently treated with an antifungal agent and nivolumab. Since there was absence of obvious immunosuppression and the presence of a drastic effect on tumour remission during nivolumab therapy, this phenomenon suggested that the trigger of CPPA progression was dependent not on immunosuppression but on a hyperreaction to microorganisms, which was similar to the immune reconstitution inflammatory syndrome caused by nivolumab. This was a thought‐provoking case in which the immune checkpoint inhibitor had a paradoxical effect for the tumour and infection.

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Anti-PD1 Antibody Treatment and the Development of Acute Pulmonary Tuberculosis

Cited by 127 publications

References 10 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

PD‐1 inhibitors for non‐small cell lung cancer patients with special issues: Real‐world evidence

Acute progression of aspergillosis in a patient with lung cancer receiving nivolumab

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