Plerixafor Plus Single-Dose Pegfilgrastim for Hematopoietic Stem and Progenitor Cell Mobilization: An Efficient and Safe Regimen In Good and Poor Mobilizer Patients
Authors: Herbert Kirsten , Demosthenous Lisa , Wiesner Glen , Link Emma , Westerman David Alan , Came Neil , Seymour John F , Prince Miles 
Published: October 2019

Abstract
Abstract 2256
Plerixafor (Mozobil®) is indicated in combination with daily filgrastim for hematopoietic stem and progenitor cell (HSPC) mobilization and subsequent autologous transplantation in patients with non-Hodgkin Lymphoma and multiple myeloma. In off-label use, pegfilgrastim (Neulasta®) is known to mobilize HSPC with a single injection. We hypothesise that pegfilgrastim is an attractive adjunct to plerixafor as a combination mobilizing regimen in both good- and poor-HSPC mobilizer patients, much like filgrastim but with the advantage to the patient of fewer injections. To-date there have been no published trials examining this combination.

Aim:
To investigate the tolerability, kinetics and efficacy of plerixafor plus pegfilgrastim for HSPC mobilization in patients with lymphoma or myeloma.

Method:
Twelve patients with lymphoma (n=10) and myeloma (n=2) underwent HSPC mobilization using single-dose pegfilgrastim (6mg SC mane D1) and nightly plerixafor (0.24 mg/kg SC nightly commencing 2200–2300hrs D3). Peripheral blood (PB) CD34+ monitoring commenced D3 and continued until the completion of apheresis. Apheresis commenced in all patients on D4. Nightly plerixafor/daily apheresis continued for up four doses/procedures, or until the target CD34+ yield (5×106/kg) was reached. CD34+ yields and kinetics were compared with historical controls mobilized with pegfilgrastim alone. Historical controls were mobilized with a single pegfilgrastim injection (6mg or 12mg SC mane D1), and PB CD34+ monitoring commenced on D4.

Patients:
Six ‘predicted poor-mobilizers’ (5 prior failed, 1 fludarabine-exposed) and 6 ‘predicted adequate-mobilizers’ were mobilized with pegfilgrastim plus plerixafor. Historical controls (n=22; 4 poor mobilizers) were mobilized with pegfilgrastim alone.

Results:
Four of 12(33%) study patients had a PB CD34+ count ≥5×106/L (our institutional threshold for collection) on D3 post-pegfilgrastim, however apheresis was commenced on D4 in all patients; all study patients surpassed this threshold by D4 (i.e. post-D3 evening dose of plerixafor). PB CD34+ counts peaked on D4 in 6/12 study patients and were sustained ≥5×106/L for 4 and 5 days in 8/12(67%) and 4/12(33%), respectively. Compared to historical controls, study patients were more heavily pre-treated (median prior regimens 2(1-4) vs. 1(0-2); P=0.002), and contained a higher proportion of poor mobilizers (50% vs. 18%; P=0.06). All study patients and 20/22 controls collected ≥2×106/kg CD34+ cells within 4 aphereses (P=0.53). Eleven of 12(92%) study patients vs. 16/22(76%) controls achieved this target after 2 apheresis procedures (P=0.37). After a maximum of 4 aphereses, there was a trend to higher median total CD34+ yields in the plerixafor plus pegfilgrastim patients compared to pegfilgrastim-alone patients; 8.0 ×106/kg (2.4-12.9 ×106/kg) vs. 4.8 (0.4-14.0 ×106/kg) (P=0.07), within a median of 1(1-4) vs. 2(1-4) collections (P=0.57). Study patients were assessed for the presence of tumor cells in the PB or apheresis product. One study patient with minimal BM involvement by lymphoplasmacytic lymphoma at baseline developed minimal detectable plasma cells in the PB and the apheresis product on D4 (post-plerixafor). One historical control patient with POEMS syndrome developed hyperleukocytosis after 12mg pegfilgrastim, which resolved without incident. The plerixafor plus pegfilgrastim combination was well tolerated: bone pain (worst grade=3, n=2), gastrointestinal symptoms (diarrhoea: worst grade=2, n=2) and facial paraesthesiae (n=3) were the most frequent adverse events. Engraftment data is currently being collected.

Conclusion:
Plerixafor plus pegfilgrastim is a simple, safe and effective HSPC mobilization regimen in myeloma and lymphoma, in both poor and good mobilizers. Comparison with historical controls suggests that the addition of plerixafor to pegfilgrastim may overcome risk factors for failed mobilization such as prior mobilization failure and heavy prior chemotherapy exposure, enabling even predicted poor mobilizer patients to achieve target CD34+ yields, often within just two apheresis procedures.

Disclosures:
Herbert: Genzyme: Research Funding, Speakers Bureau; Amgen: Speakers Bureau. Off Label Use: Pegfilgrastim was used for hematopoietic stem and progenitor cell mobilization, which is an off-label indication. The use of pegfilgrastim for this purpose is widely published. Prince: Amgen: Consultancy, Honoraria, Research Funding.