Plerixafor On Demand Associated With Chemotherapy and G-CSF: Interim Analysis Of a Prospective Study Shows Significant Improvement In PBSC Mobilization and Harvest With No Increase In Costs
Authors: Milone Giuseppe , Martino Massimo , Scalzulli Potito R , Spadaro Andrea , Di Martina Valentina , Schinocca Elena , Spina Eleonora , Di Marco Annalia , Cupri Alessandra , Tripepi Giovanni , Leotta Salvatore 
Published: October 2019

Background
To date, no prospective study on Plerixafor “on demand” in association with chemotherapy and G-CSF has been reported.

Methods
We present an interim analysis of the first prospective study in which Plerixafor (PLX) was administered “on demand”, according to a specific algorithm, in patients affected by Multiple Myeloma and Lymphoma who received high dose Cyclophosphamide (4g/m2) or DHAP plus G-CSF to mobilize PBSC. Algorithm was developed after a retrospective study done in our Institution (Blood Transfusion, 11(1):94). One hundred and twelve patients were registered in this prospective study, 111 patients were assessable for requirement of on demand PLX, 102 patients were evaluable for mobilization efficacy of“ PLX on demand” strategy, (72 patients were affected by MM and 30 by Lymphoma). A set of 240 patients receiving the same mobilizing chemotherapy (DHAP or CTX 4 gr/sqm) plus G-CSF were retrospectively studied for comparison.

Results
PLX requirement, overall, was 14.4% (16/111). PLX requirement was 21.6% in Lymphoma patients and 10.6% in MM patients (p=0.010). Failure to mobilize CD34+ cells in PB (CD34+ peak in PB < 20 x 10^6/l) was reduced by “on demand” strategy compared to conventional mobilization; from 13.0% to 3.0% (p=0.004). Failure to harvest CD34+cells (CD34+< 2x10^6/Kg) decreased from 20.9% to 4.0% (p=0.0001). Second mobilization rate in the “on demand” strategy compared to conventional mobilization decreased from 14.3% to 3.0% (p=0.03). In lymphoma stratum the “on demand strategy” resulted in a successful mobilization in 96.6% while the historical control group had a mobilization successful rate of 73.2% (p=0.007); in the MM stratum the “on demand strategy” was successful in 97.2% while the historical control had a mobilization success of 91.3% (p=0.09).
Negative Predictive Value (NPV) of the algorithm was determined in patients treated in the “on demand study” by evaluating the subgroup of patients who received the planned mobilization and did not receive PLX because, according to the algorithm, its use was not indicated. 93 patients were assessable, 93/93 had a successful mobilization (CD34+ in PB > 20x10^6/l), thus NPV was 100%.
Positive Predictive Value (PPV) of algorithm was determined in the subgroup of patients who were not treated because of drug shortage although the use of PLX was indicated (n 6). PPV was 83.4%.
Of the 10 patients where PLX use was indicated and who received at least one dose, a successful mobilization was reached in 70% (7/10) of cases and a successful harvest in 66.6% (6/10).
We estimated the cost of mobilizing and harvesting 100 patients affected by Lymphoma or Myeloma by either conventional mobilization based on chemotherapy plus G-CSF or by the PLX on demand strategy. Sum of cost of first mobilizations and of salvage mobilizations (required in patients failing the first mobilization attempt) were calculated in the two different mobilization strategies. Cost to mobilize 100 Myeloma patients was: 465,648 euros for conventional mobilization versus 423,816 euros for “on demand PLX” strategy; cost to mobilize 100 Lymphoma patients was 552,480 euros in conventional strategy versus 537,912 for “on demand PLX” strategy.

Conclusion
In association with CTX or DHAP plus G-CSF, the “on demand” use of Plerixafor in patients selected by our algorithm showed a significant improvement in mobilization of CD34+ cells and in harvest of PBSC with no increase in overall costs.

Disclosures:
No relevant conflicts of interest to declare.