Plerixafor

證據等級: L5

預測適應症: 7 個

Plerixafor: From Hematopoietic Stem Cell Mobilization to Myeloid Leukemia (Chemosensitization)

One-Sentence Summary

Plerixafor is a CXCR4 antagonist historically used with G-CSF to mobilize hematopoietic stem cells for transplantation. Among the seven indications the TxGNN model surfaced for this drug, only Myeloid Leukemia is backed by real-world evidence — the other six top-ranked predictions (including a non-disease genetic locus and a likely false positive for bronchitis) have zero supporting trials or literature. For Myeloid Leukemia, the evidence pack contains 30 registered clinical trials and 21 publications, making it the credible repurposing candidate in this dataset despite a comparatively lower raw TxGNN rank (#9976 vs. #600 for the top-scored but evidence-free prediction).

Quick Overview

Item	Content
Original Indication	Hematopoietic stem cell (HSC) mobilization, in combination with G-CSF, prior to autologous transplantation (derived from clinical-trial context; not present in a formal registry record — data gap DG002)
Predicted New Indication	Myeloid Leukemia (acute myeloid leukemia, AML) — as a chemosensitizing adjunct to induction/consolidation chemotherapy
TxGNN Prediction Score	99.02% (raw model rank #9976 of all candidates — notably lower than the top-scored but unsupported predictions)
Evidence Level	L2
Germany Market Status	Not marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Note on candidate selection: The top TxGNN-ranked predictions (indolent plasma cell myeloma, CMM7, pediatric leptomeningeal melanoma, epithelioid uveal melanoma, bronchitis, vulvar melanoma) all carry zero clinical trials and zero literature in this evidence pack, and are flagged in the source rationale as speculative or, in the case of CMM7, not a valid disease entity. This report therefore focuses on Myeloid Leukemia, the one prediction with substantive corroborating evidence.

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available for Plerixafor in this evidence pack (data gap DG002). Based on information embedded in the clinical trial records themselves, Plerixafor is a CXCR4 antagonist that is FDA-approved for mobilizing hematopoietic stem cells from the bone marrow into peripheral blood, typically in combination with G-CSF, to support autologous or allogeneic transplantation.

The proposed new indication — myeloid leukemia — is mechanistically adjacent to this original use. Acute myeloid leukemia (AML) blasts rely on the same CXCR4–CXCL12 axis to adhere to bone marrow stromal niches, where they are protected from chemotherapy. By blocking CXCR4, Plerixafor can mobilize leukemic blasts out of this protective niche and into circulation, where they become more sensitive to cytotoxic therapy — essentially the same "mobilization" pharmacology repurposed from healthy stem cells to leukemic cells.

This mechanistic hypothesis is not merely theoretical: it has been tested in over two dozen Phase 1/2 trials combining Plerixafor with standard induction/consolidation regimens (FLAG-Ida, mitoxantrone-etoposide-cytarabine, decitabine, sorafenib for FLT3-mutated AML) in both relapsed/refractory and newly diagnosed AML patients, and is the subject of a dedicated systematic review and meta-analysis (PMID 32877869). The landmark proof-of-concept study (Uy et al., Blood 2012, PMID 22308295) first established that Plerixafor-induced blast mobilization correlates with improved chemotherapy response in relapsed/refractory AML.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01435343	Phase 1/2	Completed	55	Fludarabine + idarubicin + cytarabine + G-CSF + Plerixafor induction in relapsed/refractory AML patients ≤65 years
NCT00906945	Phase 1/2	Completed	39	Plerixafor + G-CSF chemosensitization in relapsed/refractory AML
NCT00943943	Phase 1	Completed	33	Sorafenib + G-CSF + Plerixafor combination dose-finding in FLT3-mutated AML
NCT00822770	Phase 1/2	Completed	47	G-CSF + Plerixafor + busulfan/fludarabine conditioning for allogeneic transplant in AML/MDS/CML
NCT00512252	Phase 1/2	Completed	52	AMD3100 (Plerixafor) + mitoxantrone/etoposide/cytarabine (MEC) in relapsed/refractory AML — landmark chemosensitization study
NCT01352650	Phase 1	Completed	71	Decitabine + Plerixafor priming as induction/postremission therapy in AML patients ≥60 years
NCT01319864	Phase 1	Completed	20	Plerixafor as chemosensitizing agent with cytarabine/etoposide in pediatric relapsed acute leukemia/MDS
NCT01455025	Phase 1	Terminated	11	Dose-escalation of Plerixafor with induction/consolidation chemotherapy in relapsed AML
NCT02605460	Phase 2	Unknown	20	CXCR4 antagonist chemosensitization before autologous/allogeneic HSCT in acute leukemia in remission
NCT06141304	Phase 2	Unknown	28	Plerixafor + donor lymphocyte infusion for relapsed acute leukemia after allogeneic HSCT

20 additional trials (mobilization studies, transplant-conditioning regimens, and further AML chemosensitization protocols) are available in the underlying data but omitted here for brevity.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
29392425	2018	Phase 1/2	Annals of Hematology	PLERIFLAG regimen (FLAG-Ida + high-dose IV Plerixafor) in first early-relapsed/refractory AML
22308295	2012	Phase 1/2	Blood	Landmark chemosensitization study: CXCR4 antagonism with Plerixafor in 52 relapsed/refractory AML patients
32697348	2020	Phase 1	American Journal of Hematology	Sorafenib + G-CSF + Plerixafor in relapsed/refractory FLT3-ITD-mutated AML
39261603	2024	Review	Leukemia	Comprehensive review of CXCR4 as a therapeutic target in AML
32877869	2020	Systematic Review/Meta-analysis	Leukemia Research	Plerixafor + chemotherapy and/or HSCT in acute leukemia — pooled preclinical/clinical evidence
32079173	2020	Review	Biology	CXCR4 antagonists as stem cell mobilizers and therapy sensitizers in AML and glioblastoma
30654137	2019	Cohort	Biology of Blood and Marrow Transplantation	Safety/tolerability of Plerixafor within myeloablative conditioning for AML allografting
29724902	2018	Phase 1	Haematologica	Decitabine + Plerixafor in newly diagnosed older AML patients, with leukemia stem cell effect analysis
30150522	2018	Case Report	Cancers	Complete remission in refractory pediatric AML (monosomy 7) using Plerixafor + cytarabine + melphalan conditioning
38024589	2023	Case Report/Cohort	EJHaem	Concomitant multiple myeloma and CML case, contextualizing CXCR4-related stem cell biology

Germany Market Information

Plerixafor is currently not marketed in the covered jurisdiction (0 authorizations on record), so no authorization table is available.

Safety Considerations

Please refer to the package insert for safety information. Detailed TFDA/regulatory warnings, contraindications, and drug interaction data were not available in this evidence pack (data gap DG001, marked as Blocking severity — this gap currently prevents entry into the S1 safety pre-assessment stage).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Myeloid leukemia is the only prediction in this evidence pack supported by substantial clinical and mechanistic evidence — 30 registered trials (several completed Phase 1/2 studies) and a systematic review — establishing CXCR4 blockade as a validated chemosensitization strategy in AML. However, the drug is not currently marketed in the covered jurisdiction, and a blocking data gap on formal safety labeling (warnings/contraindications) prevents formal safety pre-assessment (S1).

To proceed, the following is needed:

Resolve DG001 (Blocking): obtain official product label / regulatory safety documentation (warnings, contraindications, DDI) before advancing past preliminary screening
Resolve DG002 (High): obtain formal mechanism-of-action documentation (e.g., via DrugBank API) to strengthen the mechanistic linkage analysis
Confirm original approved indication and formal regulatory history, since the current record shows no registered original indication
Given multiple terminated/unknown-status trials in the dataset, assess feasibility and reasons for discontinuation before committing further evaluation resources
Deprioritize the other six TxGNN-predicted indications (indolent plasma cell myeloma, CMM7, pediatric leptomeningeal melanoma, epithelioid uveal melanoma, bronchitis, vulvar melanoma) pending any future emergence of clinical or literature evidence — none currently warrant investment
Disclaimer

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