Dostarlimab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Dostarlimab: From Mismatch Repair-Deficient Solid Tumours to Tendinopathy
One-Sentence Summary
Dostarlimab is an anti-PD-1 monoclonal antibody (Jemperli) used in cancer immunotherapy, mainly for mismatch repair deficient (dMMR) endometrial cancer and other dMMR solid tumours. The TxGNN model lists tendinopathy as its top predicted new indication, but the score is neutral (0.5) and no clinical trials or publications support it. The evidence level is therefore L5 (model prediction only), and the recommendation is Hold.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | The Singapore licence record contains no approved indication text. Other drug reference data describe dMMR recurrent/advanced endometrial cancer and other dMMR solid tumours. |
| Predicted New Indication | Tendinopathy |
| TxGNN Prediction Score | 50.0% (neutral, uninformative) |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on pharmacology data, dostarlimab binds human PD-1 with high affinity and blocks its interaction with both PD-L1 and PD-L2. This releases the brake on T cells and enhances anti-tumour immune activity.
Honestly, the link to tendinopathy is weak. Chronic tendinopathy is a degenerative and inflammatory-remodelling condition. PD-1 blockade is more likely to worsen immune-mediated musculoskeletal inflammation than relieve it, and checkpoint inhibitors are known to cause immune-related adverse events such as arthralgia and tendinitis. The score of 0.5 carries no discriminating signal, so this prediction should be treated as a model artifact, not a biological finding.
The other nine predictions (autoimmune retinopathy, anaphylaxis and its subtypes, hypervalinemia/hyperleucine-isoleucinemia, and several epilepsy syndromes) have the same neutral score and no supporting studies. Several are mechanistically counterproductive: immune activation would be undesirable in autoimmune retinopathy, and dostarlimab itself carries hypersensitivity warnings.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16623P | JEMPERLI Concentrate for Solution for Infusion 500mg/10mL | Infusion, solution concentrate | Not stated in the licence record |
The product is an injectable (intravenous infusion) and is currently valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunotherapy (anti-PD-1 monoclonal antibody), not a conventional cytotoxic agent |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions. Immune-related adverse events are generally monitored through liver, thyroid and renal function. |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Class-related risks: Checkpoint inhibitors have been associated with immune-related adverse events, including arthralgia, tendinitis, autoimmune/paraneoplastic retinopathy and uveitis. Dostarlimab also carries infusion-related and hypersensitivity reaction warnings.
- Drug Interactions: The only interaction record is its pharmacological target, PD-1 (PDCD1). No drug-drug interaction data are available.
For full safety information, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication rests only on a neutral model score (0.5), with no clinical trials or literature. The biological reasoning suggests PD-1 blockade could worsen tendon inflammation rather than treat it. The licence record also lacks approved-indication text and package insert safety data.
To proceed, the following is needed:
- The package insert (warnings and contraindications) from the HSA website, which is a blocking gap for safety screening
- Detailed mechanism-of-action data from DrugBank
- Approved indication text for the Singapore licence
- Preclinical or mechanistic evidence for a PD-1 role in tendinopathy; without it, repurposing is not justified
- Re-ranking of predictions to find candidates with a score above neutral and a plausible immune-mediated mechanism
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.