ORCID Profile
0000-0002-3470-8686
Current Organisations
Johns Hopkins University
,
Royal College of Surgeons in Ireland
,
Beaumont Hospital
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Publisher: American Society of Clinical Oncology (ASCO)
Date: 03-2017
Abstract: Pneumonitis is an uncommon but potentially fatal toxicity of anti–programmed death-1 (PD-1) rogrammed death ligand 1 (PD-L1) monoclonal antibodies (mAbs). Clinical, radiologic, and pathologic features are poorly described. Patients who received anti–PD-1/PD-L1 monotherapy or in combination with anti–cytotoxic T-cell lymphocyte associated antigen-4 mAb were identified at two institutions (Memorial Sloan Kettering Cancer Center: advanced solid cancers, 2009 to 2014, and Melanoma Institute of Australia: melanomas only, 2013 to 2015). Pneumonitis was diagnosed by the treating investigator cases with confirmed malignant lung infiltration or infection were excluded. Clinical, radiologic, and pathologic features of pneumonitis were collected. Associations among pneumonitis incidence, therapy received, and underlying malignancy were examined with Fisher’s exact test as were associations between pneumonitis features and outcomes. Of 915 patients who received anti–PD-1/PD-L1 mAbs, pneumonitis developed in 43 (5% 95% CI, 3% to 6% Memorial Sloan Kettering Cancer Center, 27 of 578 [5%] Melanoma Institute of Australia, 16 of 337 [5%]). Time to onset of pneumonitis ranged from 9 days to 19.2 months. The incidence of pneumonitis was higher with combination immunotherapy versus monotherapy (19 of 199 [10%] v 24 of 716 [3%] P .01). Incidence was similar in patients with melanoma and non–small-cell lung cancer (overall, 26 of 532 [5%] v nine of 209 [4%] monotherapy, 15 of 417 v five of 152 [ P = 1.0] combination, 11 of 115 v four of 57 [ P = .78]). Seventy-two percent (31 of 43) of cases were grade 1 to 2, and 86% (37 of 43) improved/resolved with drug holding/immunosuppression. Five patients worsened clinically and died during the course of pneumonitis treatment proximal cause of death was pneumonitis (n = 1), infection related to immunosuppression (n = 3), or progressive cancer (n = 1). Radiologic and pathologic features of pneumonitis were erse. Pneumonitis associated with anti–PD-1/PD-L1 mAbs is a toxicity of variable onset and clinical, radiologic, and pathologic appearances. It is more common when anti–PD-1/PD-L1 mAbs are combined with anti–cytotoxic T-cell lymphocyte associated antigen-4 mAb. Most events are low grade and improve/resolve with drug holding/immunosuppression. Rarely, pneumonitis worsens despite immunosuppression, and may result in infection and/or death.
Publisher: BMJ
Date: 07-2021
Abstract: Expanding the US Food and Drug Administration–approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%–12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements) of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 12-2016
No related grants have been discovered for Jarushka Naidoo.