Lenalidomide

Evidence Level: L2

Predicted Indications: 4

Lenalidomide

Pharmacist Assessment Report

Lenalidomide: From Plasma Cell Myeloma to Myeloid Leukaemia

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 leukaemia, with 44 registered clinical trials and 19 publications currently linked to this direction. Most of the 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 (TxGNN knowledge graph; no approved indication text is recorded in the Australian licence data)
Predicted New Indication	Myeloid leukaemia
TxGNN Prediction Score	0.9949
Evidence Level	L2
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed mechanism of action data for the original indications is not available in the data compiled for this report. Based on the mechanistic rationale compiled for this prediction, lenalidomide binds cereblon (CRBN) and redirects the CRL4-CRBN E3 ubiquitin ligase to degrade the transcription factors IKZF1 and IKZF3, as well as CK1alpha. Degradation of CK1alpha underlies its activity in del(5q) MDS. Lenalidomide also activates T cells and natural killer (NK) cells, which may support activity in AML and MDS.

Myeloid leukaemia is closely related to MDS, which is already a listed indication. MDS frequently progresses to acute myeloid leukaemia (AML). Several trials have enrolled MDS and AML patients together, especially those with chromosome 5 abnormalities.

The biological rationale is strong. However, the clinical benefit in AML without del(5q) appears modest and is mostly seen in small single-arm studies.

Clinical Trial Evidence

Forty-four trials are linked to this prediction. The table shows the 10 most relevant, prioritising myeloid leukaemia-specific studies with larger enrolments. Only trials with an assessed relevance grade of A or B, or with a larger enrolment, are selected. No ANZCTR identifiers are included in the data compiled for this report.

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00831766	Phase 1/2	Completed	51	Sequential idarubicin + cytarabine followed by lenalidomide in higher-risk MDS or untreated AML; largest assessed relevant dataset but early phase
NCT00352001	Phase 1/2	Completed	37	Lenalidomide + azacitidine in advanced MDS; no randomised comparator
NCT02126553	Phase 2	Completed	29	Lenalidomide maintenance in high-risk AML in remission; single-arm, small
NCT00360672	Phase 2	Completed	27	Single-agent lenalidomide in relapsed/refractory AML or high-risk MDS with chromosome 5 abnormalities
NCT01681537	Phase 1	Completed	36	Lenalidomide + MEC chemotherapy for AML re-induction; safety and dosing
NCT01578954	Phase 1	Completed	20	Dose-finding of lenalidomide re-induction/consolidation and maintenance in adults aged 60 or over with AML
NCT01522976	Phase 2 (randomised phase II/III)	Active, not recruiting	282	Azacitidine alone vs with lenalidomide vs with vorinostat in higher-risk MDS or CMML; largest trial
NCT01358734	Phase 2	Completed	88	Randomised: lenalidomide, azacitidine then lenalidomide, or azacitidine alone in older patients with newly diagnosed AML
NCT01038635	Phase 1/2	Completed	94	Azacitidine + lenalidomide in high-risk MDS and AML
NCT04490707	Phase 3	Unknown	60	Azacitidine + lenalidomide maintenance guided by MRD in elderly or unfit AML patients; status unverified

Literature Evidence

PMID	Year	Type	Journal	Key Findings
23316859	2013	Review	Expert Opin Investig Drugs	Lenalidomide as a novel treatment for AML; approved for del(5q) low-risk MDS, with trials in higher-risk MDS and AML
32899586	2020	Review	Cancers	Role of immunomodulatory drugs, including lenalidomide, in AML treatment
39881283	2025	Preclinical	Cell Mol Biol Lett	KDM5C stabilises cereblon and increases AML cell sensitivity 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
41348013	2025	Review	Hematology ASH Educ Program	Updates in low/intermediate-risk MDS
28799436	2017	Review	Expert Rev Hematol	Immunomodulatory approaches, including IMiDs, in myelofibrosis
17488990	2007	Review	J Clin Oncol	AML and MDS in older patients

No randomised controlled trial publications specific to lenalidomide in myeloid leukaemia were identified. The literature is mainly reviews, many of which cover MDS or are only indirectly relevant.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 11029L	Lenalidomide Dr.Reddy’s	Capsule 5 mg	Not recorded in the data compiled for this report

Cytotoxicity

Item	Content
Cytotoxicity Classification	Immunomodulatory agent (thalidomide analogue) used in antineoplastic therapy; not a conventional cytotoxic
Myelosuppression Risk	Significant. Thrombocytopenia, neutropenia and agranulocytosis appear among the contraindication-related conditions recorded for this drug
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	Full blood count (with differential and platelets), renal function, and thromboembolism surveillance
Handling Protection	Please refer to the Product Information (PI) warnings and precautions. Pregnancy exposure must be strictly avoided because lenalidomide is a thalidomide analogue

Safety Considerations

Label-based warnings and contraindications are not available in the data compiled for this report.

Disease-level contraindication signals (knowledge graph, not label text): thrombocytopenia, neutropenia, agranulocytosis, pulmonary embolism, impaired renal function, cancer and embryoma.
Drug Interactions: 100 interactions were identified. Major interactions are listed with rosuvastatin and simvastatin. Moderate interactions are listed with eliglustat and naltrexone. Many others have an unclassified severity, including metformin, morphine, prednisone, omeprazole and pantoprazole.
Secondary malignancy signal: the linked literature reports lenalidomide-associated secondary B-cell acute lymphoblastic leukaemia and therapy-related myeloid neoplasms. This is relevant when considering use in haematological malignancy.

Please refer to the TGA-approved Product Information (PI) for full safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale:

Many phase 1 and 2 trials, including some randomised studies, examine lenalidomide in AML and MDS, and the biological rationale is strong. However, the studies are mostly small, single-arm and early-phase. Clinical benefit is modest outside del(5q) disease, and no completed phase 3 evidence is identified, so the evidence level is L2.

To proceed, the following is needed:

TGA Product Information, including warnings, contraindications and approved indications for ARTG 11029L
Mechanism of action data from DrugBank
Review of randomised results (for example NCT01358734 and NCT01522976) and a restriction to settings with cytogenetic selection, such as del(5q)
A monitoring plan covering myelosuppression, thromboembolism, renal function, secondary malignancy risk and pregnancy prevention
Review of the interaction profile with statins and other co-medications
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.