Midostaurin
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Midostaurin: From Acute Myeloid Leukaemia to Familial Thrombocytosis
One-Sentence Summary
Midostaurin is an oral multikinase inhibitor originally used for acute myeloid leukaemia (AML). The TxGNN model predicts it may be effective for Familial Thrombocytosis, but no clinical trials and no publications currently support this specific prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute myeloid leukaemia (including several AML subtypes) |
| Predicted New Indication | Familial thrombocytosis |
| TxGNN Prediction Score | 98.92% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, midostaurin is a multikinase inhibitor that acts on targets including FLT3, KIT and PKC. Its efficacy in AML is tied to this kinase inhibition, and mechanistically it may be applicable to certain kinase-driven blood disorders.
Familial thrombocytosis is usually caused by inherited variants in genes such as THPO, MPL or JAK2. A link to midostaurin's kinase targets is plausible, but no trial or publication was retrieved to support it. The high TxGNN score may partly reflect proximity in the knowledge network rather than a proven biological connection.
Other predictions reviewed. The 10 top-ranked predictions are listed below. Only three have any retrieved literature:
| Predicted Indication | Score | Evidence | Comment |
|---|---|---|---|
| Familial thrombocytosis | 98.92% | L5 | Prediction only |
| Reactive thrombocytosis | 98.76% | L5 | A secondary, cytokine-driven condition; kinase inhibition has no clear rationale, and the score is likely a network artifact |
| Metastatic melanoma | 97.64% | L3 | A Phase IIA study reported lack of activity |
| Inverse Klippel-Trenaunay syndrome | 97.62% | L5 | No supporting evidence |
| Thrombocythaemia | 97.48% | L4 | Only indirect evidence from myeloproliferative neoplasm reviews |
| Non-cutaneous melanoma | 97.13% | L5 | KIT-driven subsets exist, but the negative melanoma study lowers confidence |
| Epithelioid cell melanoma | 96.95% | L5 | No supporting evidence |
| Eyelid melanoma | 96.94% | L5 | No supporting evidence |
| Scrotum melanoma | 96.73% | L5 | No supporting evidence |
| Malignant melanoma of the mucosa | 96.39% | L5 | KIT alterations are more frequent, but no specific evidence was found |
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for familial thrombocytosis.
For context, the closest evidence found among the other predictions is:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16969355 | 2006 | Phase IIA trial | British Journal of Cancer | Midostaurin 75 mg three times daily was tested in 17 patients with metastatic melanoma and lacked activity (negative result) |
| 29704617 | 2018 | Review | Pharmacological Research | Reviews small-molecule KIT inhibitors in neoplastic disorders; indirect context only |
| 29277359 | 2018 | Review | Clinical Lymphoma, Myeloma & Leukemia | Update on myeloproliferative neoplasms (JAK2, MPL, CALR mutations); indirect context for thrombocythaemia |
| 23471017 | 2011 | Review | Blood Cancer Journal | Symposium proceedings on epigenetic mutations and treatment progress in myeloproliferative neoplasms; indirect context |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15518P | RYDAPT SOFT CAPSULE 25MG | Capsule, liquid filled (oral) | Not stated in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multikinase inhibitor) |
| 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 (typically blood counts, liver and renal function) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were identified in the interaction database. The first 20 retrieved include:
- Major: Clarithromycin, Dolasetron
- Moderate: Acarbose, Famotidine, Albiglutide, Alogliptin, Metformin, Pioglitazone, Loperamide, Aprepitant, Dexamethasone, Bisacodyl, Canagliflozin, Chlorpropamide, Cimetidine, Picosulfuric acid, Polyethylene glycol (3350 with electrolytes), Dapagliflozin, Saxagliptin, Dulaglutide
Please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on the model score alone (L5). No trials or publications address familial thrombocytosis. The one clinical study found for another predicted indication, metastatic melanoma, was negative. Familial thrombocytosis is rare, and its link to midostaurin's kinase targets is only theoretical.
To proceed, the following is needed:
- Mechanism of action data for midostaurin, to analyse the link to thrombocytosis-related pathways
- Package insert warnings and contraindications from the Singapore regulator (HSA), which are required before safety screening
- Preclinical or case-level evidence, such as testing in THPO-, MPL- or JAK2-variant models
- Review of whether thrombocythaemia (L4, myeloproliferative neoplasm context) is a stronger candidate than familial thrombocytosis
- Biomarker-selected evidence (for example, KIT-mutant disease) before reconsidering any melanoma indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.