Plerixafor
Table of Contents
Plerixafor: CMM7
One-Sentence Summary
Plerixafor is a CXCR4 antagonist originally used as a stem cell mobiliser in plasma cell myeloma (multiple myeloma). The data compiled for this report show considerably more evidence for a related prediction, myeloid leukaemia (25 trials, 20 publications), which is discussed below as the best-supported alternative.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | CMM7 |
| TxGNN Prediction Score | 0.9934 |
| Evidence Level | L5 (model prediction only) |
| 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 | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, plerixafor is a CXCR4 antagonist (it also interacts with ACKR3). It blocks the CXCL12/CXCR4 axis, which anchors haematopoietic and malignant cells in the protective bone marrow niche, and so mobilises them into the circulation.
Plerixafor is already used to mobilise stem cells in multiple myeloma and non-Hodgkin lymphoma before autologous transplantation. The prediction for the indolent subtype extends this link to the disease itself. However, no trials or literature were found that support an anti-myeloma or disease-modifying role in indolent disease, so the prediction currently rests on the model score alone.
The strongest mechanistic case in the data is for myeloid leukaemia. Blocking CXCR4 may release leukaemic cells from the marrow niche and sensitise them to chemotherapy. This is supported by reviews (for example PMID 39261603 and 32877869) and by multiple early-phase combination trials.
Clinical Trial Evidence
Myeloid leukaemia (best-supported alternative prediction; evidence level L2), selected from 25 trials:
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00512252 | Phase 1/2 | Completed | 52 | Plerixafor with mitoxantrone, etoposide and cytarabine in relapsed/refractory AML |
| NCT00906945 | Phase 1/2 | Completed | 39 | Plerixafor plus G-CSF as chemosensitisation in relapsed/refractory AML |
| NCT01319864 | Phase 1 | Completed | 20 | Plerixafor as chemosensitiser with cytarabine and etoposide in paediatric relapsed leukaemia/MDS |
| NCT00990054 | Phase 1 | Completed | 36 | Dose escalation with cytarabine and daunorubicin (“7+3”) in newly diagnosed AML |
| NCT01352650 | Phase 1 | Completed | 71 | Decitabine plus plerixafor priming in AML patients aged 60 years or older |
| NCT01435343 | Phase 1/2 | Completed | 55 | Fludarabine, idarubicin, cytarabine, G-CSF and plerixafor in relapsed/refractory AML |
| NCT00943943 | Phase 1 | Completed | 33 | Sorafenib with G-CSF and plerixafor in FLT3-mutated AML |
| NCT00822770 | Phase 1/2 | Completed | 47 | G-CSF and plerixafor with busulfan/fludarabine conditioning before allogeneic transplant |
| NCT01160354 | Phase 1/2 | Terminated | 22 | Plerixafor with clofarabine in older untreated AML; closed early |
| NCT06141304 | Phase 2 | Unknown | 28 | Plerixafor plus donor lymphocyte infusion for relapsed acute leukaemia after transplant |
No Australian (ANZCTR) trial identifiers were available in the data. All trials are early phase (Phase 1/2 at most), and several were terminated or have unknown status.
Literature Evidence
Indolent plasma cell myeloma: Currently no related literature available.
Myeloid leukaemia (selected from 20 publications):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32877869 | 2020 | Systematic review/meta-analysis | Leukemia Research | Plerixafor can mobilise and sensitise leukaemia cells to cytotoxic therapy in acute leukaemia |
| 39261603 | 2024 | Review | Leukemia | CXCL12-CXCR4 axis as a therapeutic target in AML |
| 22308295 | 2012 | Phase 1/2 trial | Blood | Chemosensitisation with plerixafor in 52 patients with relapsed/refractory AML |
| 29724902 | 2018 | Phase 1 trial | Haematologica | Plerixafor with decitabine in 69 older patients with newly diagnosed AML |
| 32697348 | 2020 | Phase 1 trial | Am J Hematol | Sorafenib, G-CSF and plerixafor in 28 patients with relapsed/refractory FLT3-ITD AML |
| 29392425 | 2018 | Phase 1/2 trial | Ann Hematol | PLERIFLAG regimen in early-relapsed or refractory AML |
| 30654137 | 2019 | Phase 1 trial | Biol Blood Marrow Transplant | Safety and tolerability of plerixafor with myeloablative conditioning in AML |
| 30150522 | 2018 | Case report | Cancers | Complete remission in a 4-year-old with refractory AML after plerixafor, cytarabine and melphalan conditioning |
| 32079173 | 2020 | Review | Biology | CXCR4 antagonists as stem cell mobilisers and therapy sensitisers in AML and glioblastoma |
| 34657533 | 2021 | Review | Expert Rev Hematol | Overview of drug repositioning in haematology |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10083Q | Plerixafor ARX | Injection 24 mg in 1.2 mL | Not recorded in the data compiled for this report |
Only one valid single-ingredient entry is recorded, in injectable form.
Cytotoxicity
Plerixafor is a haematopoietic stem cell mobiliser, not a cytotoxic anticancer drug, so a cytotoxicity assessment does not apply. When it is used alongside cytotoxic chemotherapy in leukaemia regimens, the handling and monitoring requirements of the partner drugs apply.
Safety Considerations
Warnings, contraindications and label-based interactions are not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for safety information.
Additional points from the data:
- Knowledge-graph contraindication signals (not label text): thrombocytopenia, impaired renal function and leukaemia. These should be verified against the PI.
- Pharmacological targets: CXCR4 and ACKR3. No drug-drug interactions with other medicines were recorded.
Conclusion and Next Steps
Decision: Hold
Rationale: Myeloid leukaemia has an L2 evidence level from Phase 1/2 trials only. It is better framed as a research question than a ready-to-adopt indication.
To proceed, the following is needed:
- Clinical or preclinical data on plerixafor in indolent myeloma or smouldering myeloma, or a decision to redirect the evaluation to myeloid leukaemia
- For myeloid leukaemia: randomised Phase 2/3 data, as current evidence is limited to small, early-phase combination studies with several terminated trials
- The approved indication text and safety information from the TGA PI for ARTG 10083Q
- Detailed mechanism of action data
- Review of the renal impairment and thrombocytopenia signals before any use in a new population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.