Abstract:Immune checkpoint inhibitors (ICIs) have made a breakthrough in cancer therapy. Patients treated with ICIs may develop immune-related adverse events (irAEs) due to the upregulated activity of the immune system. With the increasing use of ICIs, irAEs are more frequently reported and have become important challenges in many patients. Neurological irAEs, which include encephalitis, myelitis, aseptic meningitis, peripheral neuropathy, myasthenia gravis, and myositis, consist of a distinct group of neuroinflammator… Show more
“…The time to onset of dysgeusia was more random than the that for the other conditions and did not seem to follow any predictable or consistent pattern. It has been reported that dysgeusia constitutes 13% of grade 1 and 2 neurologic irAEs, 33 which are associated with stimulation of immune cells leading to nerve damage, with a hypothesis of immune response to the neuronal antigens 34‐37 . If this indeed is the case, the one might expect a more definitive trajectory than we noted in our patient cohort.…”
Background
Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune‐related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood.
Methods
Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed. Reports of oral conditions were categorized into oral mucosal disorders, xerostomia, and dysgeusia. After applying exclusion criteria, demographic characteristics and clinical features were summarized for the patients who had oral irAEs.
Results
In total, 317 patients developed oral conditions that were associated with ICIT (incidence, 6.8%; 317 of 4683 patients). These conditions included xerostomia (68.5%), oral mucosal disorders (33.4%), and dysgeusia (24.0%). In patients with oral irAEs, respiratory cancer (28.4%) was the most common primary cancer, followed by melanoma (26.2%), and head and neck cancer (14.8%). Oral mucosal disorders developed after the initiation of ICIT between 2 and 851 days (between 1 and 1332 days in patients with xerostomia and between 1 and 1455 days in patients with dysgeusia). Of all oral irAEs, 50.9% developed within 3 months, and 85.5% developed within 12 months.
Conclusions
Oral side effects appear to be more common among patients who receive ICIT than has been previously reported. Concomitant cytotoxic regimens may exacerbate the risk of oral adverse events, perhaps representing the sum of the effects of different, but simultaneous or sequential, pathogenic mechanisms. Additional studies are warranted to better characterize oral irAEs and their biologic basis.
“…The time to onset of dysgeusia was more random than the that for the other conditions and did not seem to follow any predictable or consistent pattern. It has been reported that dysgeusia constitutes 13% of grade 1 and 2 neurologic irAEs, 33 which are associated with stimulation of immune cells leading to nerve damage, with a hypothesis of immune response to the neuronal antigens 34‐37 . If this indeed is the case, the one might expect a more definitive trajectory than we noted in our patient cohort.…”
Background
Immune checkpoint inhibitors (ICIs) are increasingly accepted as a treatment option for several cancers. Although various systemic immune‐related adverse events (irAEs) have been characterized, the effect of ICIs on the oral cavity and contiguous structures is still poorly understood.
Methods
Electronic medical records of 4683 patients in the Mass General Brigham Registered Patient Data Registry who received ICI therapy (ICIT) between December 2011 and September 2019 were reviewed. Reports of oral conditions were categorized into oral mucosal disorders, xerostomia, and dysgeusia. After applying exclusion criteria, demographic characteristics and clinical features were summarized for the patients who had oral irAEs.
Results
In total, 317 patients developed oral conditions that were associated with ICIT (incidence, 6.8%; 317 of 4683 patients). These conditions included xerostomia (68.5%), oral mucosal disorders (33.4%), and dysgeusia (24.0%). In patients with oral irAEs, respiratory cancer (28.4%) was the most common primary cancer, followed by melanoma (26.2%), and head and neck cancer (14.8%). Oral mucosal disorders developed after the initiation of ICIT between 2 and 851 days (between 1 and 1332 days in patients with xerostomia and between 1 and 1455 days in patients with dysgeusia). Of all oral irAEs, 50.9% developed within 3 months, and 85.5% developed within 12 months.
Conclusions
Oral side effects appear to be more common among patients who receive ICIT than has been previously reported. Concomitant cytotoxic regimens may exacerbate the risk of oral adverse events, perhaps representing the sum of the effects of different, but simultaneous or sequential, pathogenic mechanisms. Additional studies are warranted to better characterize oral irAEs and their biologic basis.
“…3 Good clinical response following drug cessation and corticosteroids is reported; if insufficient, IVIg, plasmapheresis, infliximab, rituximab, or cyclophosphamide should be considered in refractory cases. 5,6 A selection of reported movement disorders associated with immune checkpoint inhibitors is compiled in Table 1.…”
Section: Discussionmentioning
confidence: 99%
“…The reported neurological adverse effects of PD-1 inhibitors are highly heterogeneous and include headache, myasthenic syndromes, neuropathy, encephalitis, aseptic meningitis, myopathy, myelitis, seizures, posterior reversible encephalopathy syndrome, and cerebellitis. 3,5,6 Myoclonus has not been associated with PD-1 inhibitors in either of the largest reviews to date; however, subacute myoclonus was listed as an adverse effect in one pembrolizumab drug trial. 2 A retrospective single center cohort study of 347 patients treated with the PD-1 inhibitors pembrolizumab and nivolumab reported the subacute development of neurological adverse events in 2.9% (n = 10) of patients.…”
“…They decrease immune cell co‐inhibitory signals, including the PD1 pathway, and thereby reinvigorate the patient's own anti‐tumor immunity 1 . As a counterpart, ICIs can be responsible for immune‐related adverse events (irAEs) that can affect any part of the nervous system 2 . Encephalitis is a rare but devastating irAE, affecting 0.16% of patients treated with ICIs and proving fatal in 6.3–16.7% of cases 2 .…”
mentioning
confidence: 99%
“…As a counterpart, ICIs can be responsible for immune‐related adverse events (irAEs) that can affect any part of the nervous system 2 . Encephalitis is a rare but devastating irAE, affecting 0.16% of patients treated with ICIs and proving fatal in 6.3–16.7% of cases 2 . Given that irAEs are generally responsive to immune‐modulating therapy, prompt initiation of corticosteroids should be considered for any patient treated with ICIs who presents with suggestive features, after rational exclusion of infectious differential diagnoses.…”
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