Lenalidomide
| 證據等級: L5 | 預測適應症: 6 個 |
目錄
Lenalidomide: From Multiple Myeloma / MDS with del(5q) to Myeloid Leukemia
One-Sentence Summary
Lenalidomide is a thalidomide-derived immunomodulatory drug (IMiD), established in the treatment of multiple myeloma and transfusion-dependent myelodysplastic syndrome (MDS) with isolated del(5q). The TxGNN model predicts it may also be effective for Myeloid Leukemia (AML/higher-risk MDS spectrum), with 50 clinical trials and 20 publications currently retrieved in support of this direction, though evidence quality is mixed (many trials terminated or of unknown status).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Multiple myeloma; MDS with del(5q) (based on well-established drug information — not captured in this evidence pack, see Data Gap DG002) |
| Predicted New Indication | Myeloid Leukemia |
| TxGNN Prediction Score | 99.49% (rank 5525) |
| Evidence Level | L2 (1 completed Phase 2 RCT identified; no completed Phase 3 RCT) |
| Taiwan Market Status | 未上市 (Not marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack (flagged as Data Gap DG002, High severity). Based on well-established pharmacological knowledge, lenalidomide is a second-generation IMiD (immunomodulatory imide drug) derived from thalidomide. It acts via cereblon (CRBN)-mediated ubiquitination and degradation of the transcription factors IKZF1/IKZF3, producing direct cytotoxic/anti-proliferative effects on malignant clones as well as immune-stimulatory effects (enhanced T-cell and NK-cell activity). It is already established for multiple myeloma and for red-blood-cell-transfusion-dependent MDS associated with a del(5q) cytogenetic abnormality.
MDS and AML exist on a biological continuum — MDS is a pre-leukemic clonal stem-cell disorder that frequently transforms into AML, and higher-risk MDS/CMML/AML are often studied together in the same trial programs. This is reflected in the evidence pack: the majority of the 50 retrieved trials and several review articles (e.g. PMID 37288607, PMID 24656536) explicitly discuss MDS, AML and CMML as a shared disease spectrum, frequently using lenalidomide in combination with hypomethylating agents (azacitidine) or conventional chemotherapy (cytarabine, idarubicin, mitoxantrone).
Mechanistically, lenalidomide's anti-clonal and immune-potentiating activity in del(5q) MDS plausibly extends to broader myeloid malignancies, particularly AML/MDS carrying chromosome 5 abnormalities or monosomy 5, which is the most consistent efficacy signal across the retrieved trials. However, results in non-del(5q) AML/MDS populations are more heterogeneous, with numerous Phase 1/2 studies terminated early (frequently for toxicity, slow accrual, or lack of efficacy rather than confirmed benefit), and no completed randomized Phase 3 trial confirms efficacy specifically for "myeloid leukemia" as a standalone indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00843882 | Phase 3 | Active, not recruiting | 247 | Randomized trial of lenalidomide alone vs. + epoetin alfa for major erythroid response in low-/int-1-risk MDS with symptomatic anemia |
| NCT01301820 | Phase 2 | Completed | 120 | Randomized, multicenter maintenance therapy alternating lenalidomide and azacitidine cycles in elderly AML patients in first CR |
| NCT00065156 | Phase 2 | Completed | 148 | Pivotal single-arm trial of lenalidomide monotherapy in RBC-transfusion-dependent del(5q) MDS (basis of original regulatory approval) |
| NCT01522976 | Phase 2/3 | Active, not recruiting | 282 | Randomized trial: azacitidine ± lenalidomide vs. azacitidine + vorinostat in higher-risk MDS/CMML |
| NCT02472691 | Phase 2 | Completed | 50 | Lenalidomide added to azacitidine + donor lymphocyte infusion for MDS/CMML/AML relapse after allo-SCT |
| NCT02126553 | Phase 2 | Completed | 29 | Lenalidomide maintenance in high-risk AML patients in remission |
| NCT00546897 | Phase 2 | Completed | 48 | Lenalidomide safety/efficacy in untreated AML (≥60y) without 5q abnormalities |
| NCT02538965 | Phase 2 | Completed | 17 | Lenalidomide activity/safety/PK in pediatric relapsed/refractory AML |
| NCT02921802 | N/A (post-marketing surveillance) | Completed | 4,626 | Large all-case surveillance of Revlimid 5mg capsules real-world safety/efficacy |
| NCT01016600 | Phase 1/2 | Completed | 31 | Azacitidine + lenalidomide toxicity and remission rate in AML |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30653424 | 2019 | Prospective clinical trial (JCO) | J Clin Oncol | Combination lenalidomide + azacitidine as salvage therapy for AML/MDS relapse after allo-SCT |
| 31221030 | 2019 | Systematic review & meta-analysis | Hematology (Amsterdam) | Efficacy and adverse events of azacitidine + lenalidomide across AML, MDS and CMML |
| 37259567 | 2023 | Prospective clinical trial (Azalena) | Haematologica | Azacitidine + lenalidomide + DLI for relapsed MDS/AML/CMML after allogeneic transplant |
| 37288607 | 2023 | Review | American Journal of Hematology | 2023 update on MDS diagnosis, risk-stratification and management |
| 37874917 | 2023 | Review | Blood | Clinical decision-making and treatment framework for MDS |
| 24656536 | 2014 | Review | Lancet | Overview of MDS pathophysiology, clinical course and progression to AML |
| 23644421 | 2013 | Review/Editorial | Leukemia | Rationale for combining azacitidine and lenalidomide in MDS/AML |
| 23316859 | 2013 | Review | Expert Opin Investig Drugs | Lenalidomide as a novel treatment approach in AML |
| 34955443 | 2022 | Phase Ib clinical trial | J Geriatr Oncol | Safety of lenalidomide as post-remission therapy in older AML patients |
| 39881283 | 2025 | Mechanism study | Cell Mol Biol Lett | KDM5C enhances AML sensitivity to lenalidomide by stabilizing cereblon (CRBN) |
Taiwan Market Information
Lenalidomide currently has no marketing authorization record in this evidence pack — market status is "未上市" (not marketed) with 0 licenses on file. No authorization number, product name, dosage form, or approved indication text is available for tabulation.
Cytotoxicity
Lenalidomide's original approved indications (multiple myeloma; MDS/leukemia-spectrum disorders) meet the antineoplastic criteria, so this section applies. Note: no DrugBank toxicity data or TFDA label data is present in this evidence pack (Data Gap DG001, Blocking; DG002, High) — the following reflects well-established pharmacological knowledge, not pack-sourced data, and must be confirmed against the actual package insert once obtained.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted/immunomodulatory therapy (IMiD; cereblon-mediated — not a conventional cytotoxic chemotherapy agent) |
| Myelosuppression Risk | High — neutropenia and thrombocytopenia are well documented dose-limiting toxicities requiring dose modification |
| Emetogenicity Classification | Low (typical of IMiDs, in contrast to conventional cytotoxic chemotherapy) |
| Monitoring Items | CBC with differential (weekly during early cycles), renal function (dose adjustment required — renally cleared), VTE risk assessment, pregnancy testing given teratogenicity |
| Handling Protection | Yes — lenalidomide is teratogenic (thalidomide analog); handling and dispensing require controlled-distribution/REMS-equivalent safeguards in addition to standard cytotoxic handling precautions |
Safety Considerations
Please refer to the package insert for safety information. No key warnings, contraindications, or drug-interaction data are available in this evidence pack — the TFDA package insert query (DG001) is flagged as a Blocking data gap that must be resolved before a safety initial evaluation (S1) can proceed.
Conclusion and Next Steps
Decision: Hold
Rationale: While TxGNN assigns a high prediction score (99.49%) and a substantial volume of supporting trials (50) and literature (20) exists, the trial evidence is heterogeneous — many studies are Phase 1, terminated, or of unknown status, and no completed randomized Phase 3 trial confirms efficacy specifically for myeloid leukemia. Critically, the safety data gap (DG001, Blocking) prevents completion of even the initial safety evaluation (S1), so a Go or Guardrails decision cannot be responsibly made at this time.
To proceed, the following is needed:
- TFDA package insert (warnings, contraindications) — resolve Blocking gap DG001
- DrugBank/verified mechanism-of-action data — resolve High-severity gap DG002
- Confirmation of original approved indications and licensing status (original_indications field is currently empty)
- Manual review of trial relevance grading (most trials/literature are still marked "pending" relevance in the evidence pack) to distinguish del(5q)-specific signal from general AML/MDS use
- Drug interaction (DDI) data, currently unretrieved ("not_found")
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.