Clinical Characteristics and Management of Immune Checkpoint Inhibitor-Associated Sicca Syndrome.Cancers (Basel) 2026 Jun 04; 18(11).C
Background: Immune checkpoint inhibitors (ICIs) can induce a sicca-like syndrome that differs from primary Sjögren's disease in both immunopathogenesis and clinical phenotype. Despite growing recognition of this entity, data describing real-world management and outcomes, particularly in the context of ICI discontinuation and rechallenge, remain limited. Methods: Patients with new onset of sicca syndrome or exacerbation of previous symptoms following ICI therapy were retrospectively identified and assessed. Results: Fifty-nine patients with diverse malignancies (including melanoma, gastrointestinal, genitourinary, etc.) and sicca syndrome following treatment with ICIs (most often pembrolizumab or nivolumab +/- ipilimumab) were evaluated. Acute-onset dry mouth, primarily CTCAE v6.0 grades 1 (n = 24, 40.7%) and 2 (n = 34, 57.6%), occurred at a median of 104 days after ICI initiation, sometimes with associated dry eye (n = 8, 13.6%). Most were managed conservatively with behavioral modification and over-the-counter therapies alone (n = 37, 62.7%) while others received sialagogues (n = 9, 15.3%), dexamethasone oral rinse (n = 11, 18.6%), and/or systemic corticosteroids (n = 16, 27.1%). Additional management strategies included de-escalation to ICI monotherapy (n = 5, 8.5%) or discontinued ICI (n = 6, 10.2%). Half of patients treated with corticosteroids demonstrated subjective improvement in symptoms while 75% improved following ICI discontinuation. Four patients underwent rechallenge after a median interruption of 564 days; all (n = 4) demonstrated sicca recurrence. Conclusions: In this largest cohort to date of ICI-associated sicca syndrome, we confirm frequent improvement with steroids and/or supportive care and suggest a greater than previously appreciated risk of recurrence with rechallenge.
