Description of Immune Checkpoint Inhibitor Associated Sicca-Like Syndrome from the Canadian Research Group of Rheumatology in Immuno-Oncology Database: A Case Series
Bibliographic record
Abstract
Objectives Immune checkpoint inhibitors (ICIs) are a revolutionary cancer treatment that block inhibition of T cells, promoting immune-mediated clearance of malignancies. Decreased regulation of T cells can have many off-target effects, including the development of xerostomia and xeropthalmia, also called ICI-sicca syndrome.[1] ICI-sicca syndrome appears to be pathophysiologically distinct from Sjögren’s syndrome,[2] though predictors of sicca development in ICI patients have not been well characterized. The development of Sicca Syndrome can seriously impact on patient quality of life, causing lifelong toxicity to oral and ocular health. Reporting of sicca symptoms in randomized controlled trials is not currently standard. Little is known about the clinical presentation, response to treatment, and prognosis of those who develop ICI-sicca syndrome. Our objective was to characterize sicca symptom manifestation, management, and outcomes in patients treated with ICIs using the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) prospective and retrospective cohort databases. Methods We identified 40 cases of Sicca symptoms after exposure to ICI treatment in the CanRIO database. In this study, we describe the characteristics of these cases of ICI-sicca syndrome including cancer and ICI treatment history, Sicca symptom history, other immune-related adverse events (irAEs), medical management of irAEs, and investigations undertaken. Results Of the 40 patients identified with sicca-like symptoms, 19 (47.5%) were treated with anti-PD-1 monotherapy, 15 (37.5%) with combination anti-PD-1 and anti-CTLA-4, and 6 (15%) with anti-PD-L1 monotherapy. Thirty-five records contained information on the sicca symptom CTCAE grade; of these, 15 patients (42.9%) were recorded with grade 1 sicca symptoms, 14 (40%) grade 2, and 6 (17.1%) grade 3. Only 3 patients had previously experienced sicca-like symptoms, and 32 presented with additional irAEs. Serologies showed a distinctly different pattern from Sjögren’s syndrome, with 37.9% positive for ANA, 13.8% positive for rheumatoid factor, 34.6% positive for anti-Ro, and 4.2% positive for anti-La. Of this cohort, 72.7% had management initiated specifically for sicca symptoms, including topical management, pilocarpine, systemic glucocorticoid, and ICI pause or cessation. Fourteen of 16 patients reported partial or complete resolution of their Sicca symptoms with treatment. Conclusion To date, this is the largest case series on sicca treatments and outcomes in ICI-treated patients worldwide. ICI-induced sicca, in contrast to traditional Sjögren’s syndrome, appears to be highly responsive to immunosuppressive treatments. This work characterized a wide range of treatment modalities and may assist those involved in ICI-treated patients’ care to initiate therapy and reduce the risk of serious complications of sicca syndrome. [1.] Harris J. Oral Dis 2022;28:2083-2092. [2.] Warner B. Oncologist 2019;24:1259-69.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.006 | 0.005 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".