Lenalidomide
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Lenalidomide: From Plasma Cell Myeloma to Myeloid Leukemia
One-Sentence Summary
Lenalidomide is an oral immunomodulatory drug originally used for plasma cell myeloma, mantle cell lymphoma and myelodysplastic syndrome (MDS). The TxGNN model predicts it may be effective for myeloid leukemia, with 44 clinical trials and 19 publications currently linked to this direction. Most trials are small, early-phase, or single-arm studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Plasma cell myeloma, mantle cell lymphoma, B-cell neoplasm, lymphosarcoma, myelodysplastic syndrome (the registration records contain no approved-indication text, so the original indications come from the knowledge graph) |
| Predicted New Indication | Myeloid leukemia |
| TxGNN Prediction Score | 99.49% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data was not available from the drug database for this report. Based on the mechanistic analysis compiled for this prediction, lenalidomide binds cereblon (CRBN) and redirects the CRL4-CRBN E3 ubiquitin ligase to degrade IKZF1, IKZF3 and CK1alpha. The CK1alpha degradation drives the response in del(5q) MDS. Lenalidomide also activates NK and T cells.
Myeloid leukemia is closely related to MDS, which is already an established use. MDS often progresses to acute myeloid leukemia (AML), and the two share biology such as del(5q) and immune dysregulation. Preclinical work also shows that CRBN levels influence how AML cells respond to lenalidomide (PMID 39881283).
This rationale is plausible, but the evidence in AML is weaker than in MDS. It is limited to small single-arm studies of combinations and maintenance therapy.
Clinical Trial Evidence
Forty-four trials were linked to this prediction. The 10 most relevant are listed below. Trials graded most relevant by the data review and with larger enrollment were prioritised.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00831766 | Phase 1/2 | Completed | 51 | Idarubicin + cytarabine followed by lenalidomide in MDS (RAEB-2) or untreated AML; the largest directly relevant myeloid study, supporting feasibility |
| NCT00352001 | Phase 1/2 | Completed | 37 | Lenalidomide + azacitidine in advanced MDS |
| NCT02126553 | Phase 2 | Completed | 29 | Lenalidomide maintenance in high-risk AML in remission; single-arm and small |
| NCT00360672 | Phase 2 | Completed | 27 | Single-agent lenalidomide in relapsed/refractory AML or high-risk MDS with chromosome 5 abnormalities |
| NCT01358734 | Phase 2 | Completed | 88 | Randomised comparison of lenalidomide, sequential azacitidine + lenalidomide, and azacitidine alone in older patients with newly diagnosed AML |
| NCT01301820 | Phase 2 | Completed | 120 | Alternating lenalidomide and azacitidine maintenance after LIA induction in elderly AML |
| NCT01038635 | Phase 1/2 | Completed | 94 | Azacitidine + lenalidomide in high-risk MDS and AML |
| NCT01522976 | Phase 2 | Active, not recruiting | 282 | Randomised phase II/III of azacitidine ± lenalidomide or vorinostat in higher-risk MDS/CMML |
| NCT01681537 | Phase 1 | Completed | 36 | Lenalidomide + MEC chemotherapy for AML reinduction; safety and dose-finding |
| NCT00843882 | Phase 3 | Active, not recruiting | 247 | Lenalidomide with or without epoetin alfa in low/intermediate-1 risk MDS with anemia (MDS, not AML) |
Other registered trials include post-transplant maintenance studies, a paediatric relapsed/refractory AML study (NCT02538965, n=17) and several terminated studies with very small enrollment.
Literature Evidence
No randomised trials in myeloid leukemia were retrieved for this prediction. The literature is mainly reviews, with one preclinical study.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 23316859 | 2013 | Review | Expert Opin Investig Drugs | Lenalidomide as a novel AML treatment; approved for del(5q) low-risk MDS and for myeloma, with trials in higher-risk MDS and AML |
| 39881283 | 2025 | Preclinical | Cell Mol Biol Lett | KDM5C stabilises CRBN and increases AML cell sensitivity to lenalidomide |
| 23153925 | 2013 | Review | Clin Lymphoma Myeloma Leuk | Immunomodulatory drugs as new options for MDS |
| 37288607 | 2023 | Review | Am J Hematol | MDS update on diagnosis, risk stratification and management |
| 37874917 | 2023 | Review | Blood | Clinical decision-making and treatment of MDS |
| 24656536 | 2014 | Review | Lancet | Overview of myelodysplastic syndromes |
| 29795386 | 2018 | Review | Blood Cancer J | Current MDS treatment algorithm |
| 17488990 | 2007 | Review | J Clin Oncol | AML and MDS in older patients |
| 22483153 | 2012 | Review | Curr Cancer Drug Targets | Novel and emerging drugs for AML |
| 41348013 | 2025 | Review | Hematology ASH Educ Program | Updates in low/intermediate-risk MDS |
Singapore Market Information
Twenty registrations are valid. All are single-ingredient oral capsules. No approved-indication text was available in the registration records. The five main registrations are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13663P | Revlimid Capsules 10mg (Celgene) | Capsule | Not stated in the registration record |
| SIN13662P | Revlimid Capsules 5mg (Celgene) | Capsule | Not stated in the registration record |
| SIN13664P | Revlimid Capsules 15 mg (Celgene) | Capsule | Not stated in the registration record |
| SIN13665P | Revlimid Capsules 25 mg (Celgene) | Capsule | Not stated in the registration record |
| SIN16190P | LENLI Capsules 25MG (Lotus) | Capsule | Not stated in the registration record |
Generic products are also registered, including Linadex (Hetero), Myolid (Biocon), Lenalidomide Grindeks and Lenalidomide-Teva.
Cytotoxicity
Lenalidomide is an antineoplastic drug, but it is an immunomodulatory agent rather than a conventional cytotoxic chemotherapy.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunomodulatory / targeted protein-degradation agent (thalidomide analogue), not a conventional cytotoxic |
| Myelosuppression Risk | High. Neutropenia and thrombocytopenia are listed as contraindicated conditions in the knowledge graph, and haematological toxicity is a well-known dose-limiting effect |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, renal function (impaired renal function is flagged), thromboembolism signs |
| Handling Protection | Please refer to the package insert warnings and precautions. As a thalidomide analogue with embryo-related concerns, strict pregnancy-prevention precautions are expected |
Safety Considerations
- Conditions flagged in the knowledge graph (not taken from label text): thrombocytopenia, neutropenia, agranulocytosis, pulmonary embolism, impaired renal function, cancer, embryoma.
- Drug Interactions: 100 interactions were found. The two flagged as Major are rosuvastatin and simvastatin. Eliglustat and naltrexone are Moderate. The rest, including prednisone, metformin and omeprazole, are of unknown severity.
- Safety signal in the literature: several case reports and series describe secondary B-cell acute lymphoblastic leukemia after prolonged lenalidomide maintenance in myeloma patients. This is a long-term safety concern.
The package insert warnings and contraindications could not be retrieved for this report. Please refer to the package insert for the authoritative safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Many phase 1 and 2 studies, including the larger randomised azacitidine ± lenalidomide trials, and the approved use in del(5q) MDS support biological plausibility in myeloid malignancies. However, AML-specific evidence comes from small, mostly single-arm studies, and no completed phase 3 trial in myeloid leukemia was found. Haematological toxicity and secondary-malignancy signals call for careful patient selection.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA (currently missing and blocking safety screening)
- Mechanism-of-action data from the drug database
- Published results and outcomes from the randomised trials (e.g. NCT01358734, NCT01522976) to confirm the benefit in AML
- A haematological monitoring and risk-management plan, including pregnancy-prevention measures
- Review of the Major statin interactions and long-term secondary-malignancy surveillance
Other Predicted Indications (Brief)
| Predicted Indication | Evidence Level | Recommendation | |------|------|------| | Unclassified myelodysplastic syndrome | L3 | Research Question (evidence mostly in the del(5q) subset) | | Lymph node cancer | L3 | Research Question (the linked trial is in prostate cancer and is not relevant) | | Acute lymphoblastic leukemia | L3 | Hold (small early studies; secondary B-ALL safety signal) | | Refractory cytopenia of childhood | L4 | Hold | | Aregenerative anemia | L4 | Hold | | Blast phase CML, BCR-ABL1 positive | L4 | Hold | | Severe congenital hypochromic anemia with ringed sideroblasts | L5 | Hold | | Partial deletion of the long arm of chromosome 5 | L5 | Hold (largely covered by the approved del(5q) MDS use) | | Ganglioneuroblastoma | L5 | Hold |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.