Lenalidomide
| Evidence Level: L2 | Predicted Indications: 4 |
Table of Contents
Lenalidomide: Myeloid leukemia
One-Sentence Summary
Lenalidomide is an oral immunomodulatory drug originally used to treat plasma cell myeloma, mantle cell lymphoma and myelodysplastic syndrome. The TxGNN model predicts it may be effective for myeloid leukemia, with 47 clinical trials (mostly Phase 1 and Phase 2) and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Myeloid leukemia |
| TxGNN Prediction Score | 0.9949 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data for lenalidomide is not available in the data compiled for this report. Based on general knowledge, lenalidomide is a cereblon E3 ligase modulator. It promotes degradation of the transcription factors IKZF1 and IKZF3, and of CK1alpha, which matters in del(5q) myeloid disease. It also activates NK and T cells.
Its efficacy in plasma cell myeloma and myelodysplastic syndrome is established. Myelodysplastic syndrome is closely related to acute myeloid leukemia, because it carries a risk of transforming into it. The CK1alpha-degradation mechanism gives a plausible reason for activity in del(5q) AML and MDS. The immune-activating effects also support its use as maintenance or combination therapy. Most of the trials listed below test exactly these settings.
Other predicted indications are weaker. Unclassified MDS has only cohort and case-report literature. Refractory cytopenia of childhood has a single pediatric Phase 1 study. Aregenerative anemia is supported mainly by myeloma and lymphoma papers that are not relevant to it. Severe congenital hypochromic anemia with ringed sideroblasts has no studies at all. Del(5q) has a strong biological rationale but is a cytogenetic finding, not a stand-alone clinical indication.
Clinical Trial Evidence
The 10 most relevant trials, selected from 47 registered for myeloid leukemia:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00360672 | Phase 2 | Completed | 27 | Single-agent lenalidomide in relapsed/refractory AML or high-risk MDS with chromosome 5 abnormalities; directly on target but small and single-arm |
| NCT02126553 | Phase 2 | Completed | 29 | Lenalidomide maintenance in high-risk AML in remission; directly relevant but small and single-arm |
| NCT00831766 | Phase 1/2 | Completed | 51 | Idarubicin and cytarabine followed by lenalidomide in higher-risk MDS or untreated AML |
| NCT00352365 | Phase 2 | Completed | 41 | Lenalidomide in untreated del(5q) AML in patients aged 60 or older who declined induction chemotherapy |
| NCT00546897 | Phase 2 | Completed | 48 | Lenalidomide in untreated AML without 5q abnormalities in patients aged over 60 |
| NCT01358734 | Phase 2 | Completed | 88 | Randomized comparison of lenalidomide, sequential azacitidine plus lenalidomide, and azacitidine alone in older patients with newly diagnosed AML |
| NCT01301820 | Phase 2 | Completed | 120 | Maintenance with alternating lenalidomide and azacitidine cycles after induction in elderly fit AML patients |
| NCT01038635 | Phase 1/2 | Completed | 94 | Azacitidine plus lenalidomide in high-risk MDS and AML |
| NCT01522976 | Phase 2/3 | Active, not recruiting | 282 | Randomized comparison of azacitidine with lenalidomide, with vorinostat, or alone in higher-risk MDS and CMML |
| NCT04490707 | Phase 3 | Unknown | 60 | Azacitidine plus lenalidomide maintenance guided by MRD monitoring in elderly or unfit AML patients |
Literature Evidence
| 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 myeloma, with trials ongoing in higher-risk MDS and AML |
| 32899586 | 2020 | Review | Cancers | Immunomodulatory drugs (IMiDs) in AML treatment, covering their immunomodulatory, antiangiogenic and proapoptotic properties |
| 39881283 | 2025 | Preclinical study | Cell Mol Biol Lett | KDM5C stabilizes cereblon and increases the sensitivity of AML cells to lenalidomide |
| 37288607 | 2023 | Review | Am J Hematol | 2023 update on MDS diagnosis, risk stratification and management |
| 42400116 | 2026 | Review | Am J Hematol | 2026 update on MDS diagnosis, risk stratification and management |
| 37874917 | 2023 | Review | Blood | Clinical decision-making and treatment in MDS |
| 29795386 | 2018 | Review | Blood Cancer J | Current MDS treatment algorithm |
| 38066862 | 2023 | Review | Hematology ASH Educ Program | Next-generation therapy for lower-risk MDS |
| 20416083 | 2010 | Meeting review | J Hematol Oncol | Novel agents and regimens for AML from the 2009 ASH meeting |
| 17488990 | 2007 | Review | J Clin Oncol | AML and MDS in older patients |
The literature is mostly reviews. No randomized controlled trial of lenalidomide in myeloid leukemia was found among the publications provided.
India Market Information
The 20 valid single-ingredient registrations have no approved indication text on file. The five below are examples:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 100230 | Giolen 10mg Capsule (Innova Formulations) | Strip of 30 capsules | Not available |
| 122393 | Lenmid 25mg Tablet (Cipla) | Strip of 10 tablets | Not available |
| 123458 | Laviat 10mg Capsule (Zydus Cadila) | Strip of 10 capsules | Not available |
| 124068 | Lenome 5mg Capsule (Intas) | Strip of 30 capsules | Not available |
| 122993 | Lenalid 15 Capsule (Natco) | Bottle of 30 capsules | Not available |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Immunomodulatory agent (thalidomide analogue, cereblon modulator); not a conventional cytotoxic |
| Myelosuppression Risk | High. The knowledge graph lists thrombocytopenia, neutropenia and agranulocytosis as contraindication-related conditions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count with differential, renal function; also monitor for venous thromboembolism, since pulmonary embolism is flagged |
| Handling Protection | Please refer to the package insert warnings and precautions. Because it is a thalidomide analogue, pregnancy-prevention precautions should be considered |
Safety Considerations
- Disease-level contraindication flags (knowledge graph, not label text): thrombocytopenia, neutropenia, agranulocytosis, pulmonary embolism, impaired renal function, cancer, embryoma.
- Drug Interactions: 347 interactions were recorded. Major-level interactions include rosuvastatin and simvastatin. Moderate-level interactions include eliglustat and naltrexone. Many others have an unspecified severity level.
Please refer to the package insert for warnings and label contraindications, which were not available for this report.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Several completed Phase 2 trials, including single-agent studies in AML and maintenance studies, support activity in myeloid leukemia. Lenalidomide is already marketed in India. However, the trials are small and mostly single-arm, there is no completed Phase 3 randomized trial, and the published literature is mainly reviews. The supporting data therefore remain exploratory, and the highest-risk populations (older patients, cytopenias, renal impairment) need safeguards.
To proceed, the following is needed:
- Indian package insert warnings and contraindications, which are a blocking gap for safety screening
- Confirmed mechanism of action data from DrugBank
- Results from the randomized Phase 2/3 and Phase 3 trials (NCT01522976, NCT04490707), and a focused review of the randomized evidence in AML
- A safety plan covering myelosuppression, thromboembolism, renal dosing, and the statin interactions
- Definition of the target population, such as del(5q) disease, post-transplant maintenance, or combination with azacitidine
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.