Evidence of dryness (reflectance) and swelling (erythema) of the mucosa of the palate (and spp

Evidence of dryness (reflectance) and swelling (erythema) of the mucosa of the palate (and spp.; he was treated with antibiotics, irrigation of the parotid ducts, and eventual sialoendoscopic dilation of his ductal strictures. of CD3+ T cells with a slight predominance of CD4+ over CD8+ T cells. ICI targets (e.g., programmed cell death 1 and PD\L1) were variably positive. In direct response to the arrival of the sicca immune\related adverse event, the ICI was held in 12 individuals and corticosteroids were initiated in 10. Subjective improvement in symptoms was accomplished in the majority; however, salivary secretion remained very low. Summary. ICI therapy is definitely associated with an autoimmune\induced sicca syndrome unique from Sj?gren’s syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular injury. Improvement can be achieved having a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary circulation deficits may be long term. Implications for Practice. Sicca syndrome Asenapine HCl has been reported as an immune\related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies shown mild\to\severe sialadenitis unique from Sj?gren’s syndrome, with diffuse T\cell lymphocytic infiltration and acinar injury. Acknowledgement of the cardinal features of ICI\induced sicca will spur appropriate medical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine professionals better identify individuals that develop ICI\induced sicca to initiate appropriate medical evaluation and therapy to reduce the likelihood of long term salivary gland dysfunction. = 10) (= 6) (= 4) Avelumab (= 8) (= 5) (n?=?4) / (= 2) M7824 1 (PD\L1) ? (= 1) 4 19 6 ICI 70 Sj?gren A( SSA)LSGB \8 CD3+ T ITGB4 CD4+ CD8+ T ICI ( 1 PD\L1)12 ICI 10 = 16; Table ?Table1)1) and recurrent respiratory papillomatosis (RRP; = 4). Four individuals had evidence of autoimmune disease prior to ICI therapy (Table ?(Table1).1). When seen at NIH, the individuals were undergoing treatment with avelumab (= 8), nivolumab (= 5), pembrolizumab (= 4), the mixtures of nivolumab and ipilimumab (= 2), and M7824, a bifunctional fusion protein focusing on PD\L1 and transforming growth element ? (= 1). One individual (individual 4) received combination pembrolizumab/ipilimumab in the beginning but was only receiving pembrolizumab at the time of his sicca evaluation. The ICI was given in combination with enzalutamide (individual 12), a proprietary combinatorial PD\1\centered therapy (individual 10), and epacadostat or placebo (individual 5). Two individuals had a previous course of ICI treatment; one with ipilimumab (patient 3), and one with pembrolizumab (patient 9), in each stopped at least 1 year before the current one. Table 1. Clinical features of patients, underlying neoplasm, ICI treatment, and tumor response Open in a separate window aThe patient received the combination of ipilimumab and reduced\dose pembrolizumab and subsequently developed irAEs prior to starting single\agent pembrolizumab, the treatment he was receiving when evaluated at NIH. bThe patient’s best response was SD but ultimately progressed after 295 days. cPositive for polyarthritis, moderate sicca, rheumatoid factor, and anti\SSA antibodies. Abbreviations: CR, complete remission; F, female; ICI, immune checkpoint inhibitor; M, male; PD, progressive disease; PD\L1, programmed cell death ligand 1; PR, partial remission; SD, stable disease; TGF, transforming growth factor. The RECIST tumor responses to ICI therapy in the 16 patients with metastatic disease included complete remission in 3, partial remission in 2, stable disease in 6, progressive disease in 3, and noncomplete remission/nonprogressive disease in 2. Sicca Syndrome Dry mouth was a new symptom in 18 and an exacerbation of an existing one in 2 patients. The dry mouth was typically abrupt in onset and, in most, required that the patient drink water to chew and swallow dry foods. Physician\reported CTCAE severity for dry mouth was grade 2 in 15 patients and grade 1 in 5 patients, as rated by symptom criteria alone (Table ?(Table2).2). The symptoms were.Increased inter\ and intralobular fibrosis as highlighted by Masson trichrome staining (blue) relative to the healthy volunteer is evident. lymphocytic infiltration and architectural distortion. There were lymphocytic aggregates in eight patients, composed mainly of CD3+ T cells with a slight predominance of CD4+ over CD8+ T cells. ICI targets (e.g., programmed cell death 1 and PD\L1) were variably positive. In direct response to the introduction of the sicca immune\related adverse event, the ICI was held in 12 patients and corticosteroids were initiated in 10. Subjective improvement in symptoms was achieved in the majority; however, salivary secretion remained very low. Conclusion. ICI therapy is usually associated with an autoimmune\induced sicca syndrome distinct from Sj?gren’s syndrome, often abrupt in onset, usually developing within the first 3 months of treatment, and associated with sialadenitis and glandular Asenapine HCl injury. Improvement can be achieved with a graded approach depending on severity, including withholding the ICI and initiating corticosteroids. However, profound salivary flow deficits may be long term. Implications for Practice. Sicca syndrome has been reported as an immune\related adverse event (irAE) of immune checkpoint inhibitor therapy (ICI) for neoplastic diseases. Severe dry mouth (interfering with eating or sleeping) developed abruptly, typically within 90 days, after initiation of ICI therapy. Salivary gland biopsies exhibited mild\to\severe sialadenitis distinct from Sj?gren’s syndrome, with diffuse T\cell lymphocytic infiltration and acinar injury. Recognition of the cardinal features of ICI\induced sicca will spur appropriate clinical evaluation and management, including withholding of the ICI and corticosteroid, initiation. This characterization should help oncologists, rheumatologists, and oral medicine specialists better identify patients that develop ICI\induced sicca to initiate appropriate clinical evaluation and therapy to reduce the likelihood of permanent salivary gland dysfunction. = 10) (= 6) (= 4) Avelumab (= 8) (= 5) (n?=?4) / (= 2) M7824 1 (PD\L1) ? (= 1) 4 19 6 ICI 70 Sj?gren A( SSA)LSGB \8 CD3+ T CD4+ CD8+ T ICI ( 1 PD\L1)12 ICI 10 = 16; Table ?Table1)1) and recurrent respiratory papillomatosis (RRP; = 4). Four patients had evidence of autoimmune disease prior to ICI therapy (Table ?(Table1).1). When seen at NIH, the patients were undergoing treatment with avelumab (= 8), nivolumab (= 5), pembrolizumab (= 4), the combinations of nivolumab and ipilimumab (= 2), and M7824, a bifunctional fusion protein targeting PD\L1 and transforming growth factor ? (= 1). One patient (patient 4) received combination pembrolizumab/ipilimumab initially but was only receiving pembrolizumab at the time of his sicca evaluation. The ICI was given in combination with enzalutamide (patient 12), a Asenapine HCl proprietary combinatorial PD\1\based therapy (patient 10), and epacadostat or placebo (patient 5). Two patients had a prior course of ICI treatment; one with ipilimumab (patient 3), and one with pembrolizumab (patient 9), in each stopped at least 1 year before the current one. Table 1. Clinical features of patients, underlying neoplasm, ICI treatment, and tumor response Open in a separate window aThe patient received the combination of ipilimumab and reduced\dose pembrolizumab and subsequently developed irAEs prior to starting single\agent pembrolizumab, the treatment he was receiving when evaluated at NIH. bThe patient’s best response was SD but ultimately progressed after 295 days. cPositive for polyarthritis, moderate sicca, rheumatoid factor, and anti\SSA antibodies. Abbreviations: CR, complete remission; F, Asenapine HCl female; ICI, immune checkpoint inhibitor; M, male; PD, progressive disease; PD\L1, programmed cell death ligand 1; PR, partial remission; SD, stable disease; TGF, transforming growth factor. The RECIST tumor responses Asenapine HCl to ICI therapy in the 16 patients with metastatic disease included complete remission in 3, partial remission in 2, stable disease in 6, progressive disease in 3, and noncomplete remission/nonprogressive disease in 2. Sicca Syndrome Dry mouth was a new symptom in 18 and an exacerbation of an existing one in 2 patients. The dry mouth was typically abrupt in onset and, in most, required that the patient drink water to chew and swallow dry foods. Physician\reported CTCAE severity for dry mouth was grade 2 in 15 patients and grade 1 in 5 patients, as rated by symptom criteria alone (Table ?(Table2).2). The symptoms were often worse with physical exertion or at night, with patients awakening at night with their tongue stuck to.