Plerixafor plus pegfilgrastim is a safe, effective mobilization regimen for poor or adequate mobilizers of hematopoietic stem and progenitor cells: a phase I clinical trial

• Published in: Bone marrow transplantation (Basingstoke) Vol. 49; no. 8; pp. 1056 - 1062
• Main Authors: Herbert, K E, Demosthenous, L, Wiesner, G, Link, E, Westerman, D A, Came, N, Ritchie, D S, Harrison, S, Seymour, J F, Prince, H M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-08-2014; Nature Publishing Group
• Subjects: 692/308/2779/109/1940; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-HIV Agents - administration & dosage; Apheresis; Autografts; Biological and medical sciences; Blood Component Removal - methods; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; CD34 antigen; Cell Biology; Cells (biology); Diarrhea; Female; Filgrastim; Flow cytometry; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematology; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic stem cells; Heterocyclic Compounds - administration & dosage; Humans; Internal Medicine; Lymphoma; Lymphoma - therapy; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - therapy; Myeloma; original-article; Pain; Peripheral blood; Peripheral Blood Stem Cell Transplantation; Polyethylene Glycols; Progenitor cells; Public Health; Recombinant Proteins - administration & dosage; Stem cell transplantation; Stem Cells; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Tumor cells; Hematology; Plerixafor; Stem cell; Cytokine; Hematopoietic cell; Immunomodulator; Mobilization; Granulocyte colony stimulating factor; Immunostimulant agent; Pegfilgrastim; Efficiency; Phase I trial; Antagonist; Pegylated form; Therapeutic protocol; CXCR4 chemokine receptor
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2014.112

The safety, kinetics and efficacy of plerixafor+pegfilgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization are poorly understood. We treated 12 study patients (SP; lymphoma
n
=10 or myeloma
n
=2) with pegfilgrastim (6 mg SC stat D1) and plerixafor (0.24 mg/kg SC nocte from D3). Six SP were ‘predicted poor-mobilizers’ and six were ‘predicted adequate-mobilizers’. Peripheral blood (PB) CD34
+
monitoring commenced on D3. Apheresis commenced on D4. Comparison was with 22 historical controls (HC; lymphoma
n
=18, myeloma
n
=4; poor mobilizers
n
=4), mobilized with pegfilgrastim alone. Eight (67%) SP had PB CD34
+
count ⩽5 × 10
6
/L D3 post pegfilgrastim; all SP surpassed this threshold the morning after plerixafor. In SP, PBCD34
+
counts peaked D4 6/12 (50%), remaining ⩾5 × 10
6
/L for 4 days in 8/12 (67%). All SP successfully yielded target cell numbers (⩾2 × 10
6
/kg) within four aphereses. After maximum four aphereses, median total CD34+ yield was higher in SP than HC; 8.0 (range 2.4–12.9) vs 4.8 (0.4–14.0) × 10
6
/kg (
P
=0.04). Seven of twelve (58%) SP achieved target yield after one apheresis. Flow cytometry revealed no tumor cells in PB or apheresis product of SP. Plerixafor+pegfilgrastim was well tolerated with bone pain (
n
=2), diarrhoea (
n
=2) and facial paraesthesiae (
n
=3). Plerixafor+pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers, and is superior to pegfilgrastim alone.