Plerixafor

證據等級: L5

預測適應症: 7 個

Plerixafor: From Stem Cell Mobilization to Myeloid Leukemia Chemosensitization

One-Sentence Summary

Plerixafor is a CXCR4 antagonist originally used to mobilize hematopoietic stem cells for transplantation in lymphoma and multiple myeloma patients. Among several TxGNN-predicted indications for this drug, myeloid leukemia (AML) chemosensitization is the only candidate with substantial supporting evidence, with 30 clinical trials and 20 publications currently on record. (Note: TxGNN's single highest-scoring prediction, indolent plasma cell myeloma at 99.97%, currently has zero supporting trials or literature and was screened out.)

Quick Overview

Item	Content
Original Indication	Hematopoietic stem cell mobilization (with G-CSF) prior to autologous transplantation — no structured license record available in this evidence pack
Predicted New Indication	Myeloid Leukemia (AML) — chemosensitization / leukemic stem cell mobilization
TxGNN Prediction Score	99.02%
Evidence Level	L2
Finland Market Status	✗ Not marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Plerixafor is a CXCR4 antagonist that blocks the CXCL12(SDF-1)/CXCR4 signaling axis. Its original approved pharmacology disrupts the interaction between hematopoietic stem cells and their protective bone marrow niche, releasing them into peripheral blood so they can be collected for transplantation.

Myeloid leukemia cells (AML blasts and leukemic stem cells) use this same CXCR4/SDF-1 interaction to anchor themselves in protective bone marrow niches, where they evade chemotherapy and drive relapse. The mechanistic hypothesis — extensively tested in investigator-initiated trials since the AMD3100 era (plerixafor's original development code) — is that blocking CXCR4 mobilizes leukemic cells out of this protective niche, sensitizing them to concurrent chemotherapy (cytarabine, daunorubicin, decitabine, sorafenib, clofarabine, etc.).

This is a direct mechanistic extension of the drug's known pharmacology rather than an unrelated repurposing hypothesis, which is reflected in the depth of clinical investigation already performed (multiple Phase 1/2 studies across pediatric and adult AML/MDS populations spanning 2004–2026).

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT01236144	Phase 1/2	Completed	113	AML18 pilot combining TKI AC220, CXCR4 inhibitor plerixafor, or HSP90 inhibitor ganetespib with standard DAE chemotherapy in older AML/high-risk MDS patients
NCT01352650	Phase 1	Completed	71	Decitabine + plerixafor priming in AML patients ≥60 years, testing mobilization of leukemic stem cells to improve treatment outcomes
NCT01435343	Phase 1/2	Completed	55	FLAG-Ida + plerixafor induction in young patients with relapsed/refractory AML
NCT00512252	Phase 1/2	Completed	52	AMD3100 (plerixafor) + mitoxantrone/etoposide/cytarabine (MEC) in relapsed/refractory AML; hypothesis that disrupting AML–marrow niche interaction enhances chemotherapy cytotoxicity
NCT00822770	Phase 1/2	Completed	47	G-CSF + plerixafor with busulfan/fludarabine preparative regimen before allogeneic transplant for AML, MDS, and CML
NCT00990054	Phase 1	Completed	36	Dose-escalation of plerixafor with cytarabine/daunorubicin ("7+3") in newly diagnosed AML, with/without G-CSF
NCT00943943	Phase 1	Completed	33	G-CSF + plerixafor + sorafenib in FLT3-mutated AML; determined most tolerable combination dose
NCT01319864	Phase 1	Completed	20	Plerixafor as a chemosensitizing agent with cytarabine/etoposide in pediatric relapsed AML and MDS
NCT01141543	N/A	Completed	12	Plerixafor added to myeloablative preparative regimen to mobilize residual leukemic stem cells before allografting in AML
NCT01068301	Phase 1	Completed	12	Plerixafor-containing regimen in pediatric patients undergoing a second allogeneic stem cell transplant for refractory hematologic malignancy

Literature Evidence

PMID	Year	Type	Journal	Key Findings
29392425	2018	RCT (Phase I-II)	Annals of Hematology	PLERIFLAG regimen (plerixafor + FLAG-Ida) in first early-relapsed/refractory AML; plerixafor added as chemosensitizer via SDF-1α/CXCR4 blockade
32697348	2020	RCT (Phase 1)	American Journal of Hematology	Sorafenib + G-CSF + plerixafor in relapsed/refractory FLT3-ITD-mutated AML (28 patients, 3 dose levels)
22308295	2012	Phase 1/2 trial	Blood	Chemosensitization with plerixafor in 52 patients with relapsed/refractory AML; foundational trial for the CXCR4-blockade chemosensitization hypothesis
32877869	2020	Systematic Review & Meta-analysis	Leukemia Research	Pooled preclinical and clinical evidence for plerixafor + chemotherapy/HCT in acute leukemia to inform design of definitive trials
29724902	2018	Phase 1 trial	Haematologica	Plerixafor combined with decitabine in newly diagnosed older AML patients (69 treated); evaluated effect on leukemia stem cells
39261603	2024	Review	Leukemia	Comprehensive review of the CXCL12-CXCR4 axis as a therapeutic target in AML
30654137	2019	Cohort	Biology of Blood and Marrow Transplantation	Safety/tolerability of plerixafor within myeloablative conditioning for AML patients undergoing allogeneic HCT
32079173	2020	Review	Biology	CXCR4 antagonists as stem cell mobilizers and chemotherapy sensitizers in AML and glioblastoma
30150522	2018	Case Report	Cancers	Complete remission of refractory pediatric AML (monosomy 7) after a plerixafor + cytarabine + melphalan conditioning regimen
28718760	2018	Cohort	Leukemia & Lymphoma	CD25 expression and outcomes in older AML patients treated with plerixafor + decitabine

Finland Market Information

Plerixafor is currently not marketed in Finland — no marketing authorization records are on file (0 authorizations).

Safety Considerations

Please refer to the package insert for safety information. (TFDA/Fimea warnings, contraindications, and drug interaction data were not available in this evidence pack — flagged as a blocking data gap.)

Conclusion and Next Steps

Decision: Hold

Rationale: The CXCR4-blockade chemosensitization mechanism is well-supported by a large body of Phase 1/2 investigator-initiated trials and a systematic review, but no completed Phase 3 RCT has confirmed clinical benefit, and several trials were terminated or withdrawn (e.g., NCT01455025, NCT01027923, NCT00396968). Plerixafor is also not currently marketed in Finland for any oncology indication. This remains a research-stage hypothesis rather than a repurposing-ready candidate. Separately, TxGNN's highest-scoring prediction for this drug (indolent plasma cell myeloma) and four other top-6 candidates have no clinical trial or literature support and were screened to Hold at S0.

To proceed, the following is needed:

TFDA/Fimea package insert data (warnings, contraindications, DDI) to complete the S1 safety pre-screen (currently blocking)
Confirmed original MOA/indication documentation from DrugBank (currently a data gap)
A completed Phase 2/3 RCT with survival or remission endpoints to upgrade evidence from L2
Assessment of the Finland regulatory pathway, since the drug is not currently marketed
Disclaimer

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