Ribociclib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ribociclib: From Breast Cancer to Myeloid Leukemia
One-Sentence Summary
Ribociclib is an oral CDK4/6 inhibitor marketed in Singapore as Kisqali. It is used for hormone receptor-positive, HER2-negative breast cancer. The TxGNN model predicts it may be effective for myeloid leukemia, but there are 0 clinical trials and only 1 relevant preclinical publication supporting this direction, so the prediction rests mainly on the model score.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | The Singapore licence record has no indication text. The compiled literature and trials show use in HR+/HER2- breast cancer. |
| Predicted New Indication | Myeloid leukemia |
| TxGNN Prediction Score | 99.35% |
| Evidence Level | L4 (preclinical evidence only) |
| 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. Ribociclib is a selective CDK4/6 inhibitor. CDK4/6 drives cell-cycle progression, and blocking it halts proliferation in tumour cells that depend on this pathway. Its efficacy in HR+/HER2- breast cancer has been shown in large Phase 3 trials.
Because CDK4/6 also drives the cell cycle in leukemic cells, the prediction is biologically plausible. One 2020 preclinical study (PMID 32560251) reports that CDK4/6 inhibitors can target pharmacokinetic drug resistance in acute myeloid leukemia (AML) cells. That resistance involves overexpression of the ABCB1 and ABCG2 transporters. The finding is indirect and in vitro, and it does not show that ribociclib treats AML in patients.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32560251 | 2020 | Preclinical/In vitro | Cancers | CDK4/6 inhibitors may counter transporter-mediated (ABCB1/ABCG2) drug resistance in AML cells |
A second retrieved publication (PMID 41641105, a 2026 vulvar adenocarcinoma case report) is not relevant to myeloid leukemia and is excluded.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15407P | KISQALI FILM-COATED TABLET 200MG | Tablet, film coated | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (CDK4/6 inhibitor) |
| Myelosuppression Risk | Medium to high. The literature reports neutropenia, leukopenia and thrombocytopenia as common haematological adverse events. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function, electrolytes, and ECG (QT interval), as the literature reports QT prolongation, transaminase elevation and arrhythmia |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were identified. Two are rated Major: clarithromycin and dolasetron. Many are rated Moderate, including famotidine, cimetidine, metformin, pioglitazone, saxagliptin, aprepitant, loperamide, alosetron, bisacodyl, and several corticosteroids (dexamethasone, hydrocortisone, betamethasone, triamcinolone, budesonide). Published reviews note that CYP3A4 metabolism makes clinically relevant interactions likely.
- Other signals from the literature: QT prolongation, thrombotic events, pneumonitis and hematological toxicity have been reported with CDK4/6 inhibitors.
Please refer to the package insert for key warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The only support for myeloid leukemia is a high model score plus one indirect preclinical study, with no clinical trials. Ribociclib also causes myelosuppression, which is a particular concern in a bone marrow malignancy. The other top-ranked predictions are weak. Those for thrombocytopenia and related platelet disorders most likely reflect adverse-event associations rather than treatment signals. The breast carcinoma prediction is an already-approved use and not a new repurposing candidate.
To proceed, the following is needed:
- Mechanism of action data to support the mechanistic-link analysis
- The Singapore package insert (warnings, contraindications and approved indications) for safety screening
- In vivo and in vitro studies of ribociclib in AML and other myeloid leukemia models
- A review of haematological safety in leukemia patients, given the myelosuppression risk
- A CYP3A4 interaction and QT risk assessment for any leukemia treatment regimen
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.