The Use Of Plerixafor In Hard-To-Mobilize Lymphoma and Multiple Myeloma Patients Not Only Provide Sufficient Numbers Of Pbpcs To Proceed To High Dose Therapy, But Also Have a Positive Impact On Survival
Authors: Josefsen Dag , Hetland Geir , Fløisand Yngvar , Holte Harald , Kvalheim Gunnar 
Published: October 2019

Abstract
High dose therapy followed by autologous stem cell support (HDT) is a curative treatment in selected lymphoma patients. Moreover, HDT has been shown to significantly increase progression-free survival in multiple myeloma (MM) patients. To obtain a quick and sustained engraftment after high dose therapy, a minimal number of 2x106 CD34+ cells/kg are desirable. However, in 15-20% of the lymphoma and MM patients insufficient numbers of CD34+ cells are harvested. These patients, characterized as poor mobilizers, will either be considered for remobilization, or can not be offered high dose therapy. Furthermore, previous findings have shown that poorly mobilizing lymphoma patients given HDT have a less favorable prognosis than good mobilizers. Recently, new mobilizing agents including plerixafor, a CXCR4 antagonist, have been developed. We, like others, have demonstrated that with a low concentration of CD34+ cells (5-10 cells/µL) and a total white cell count >10x109/L, addition of plerixafor resulted in successful stem cell harvesting in these poor mobilizing patients. However, little is known about the clinical outcome following high dose therapy of hard to mobilize patients given plerixafor.
In the present study, we have mobilized and harvested 29 poor-mobilizers from January 2010 to December 2012, including 17 lymphoma patients and 12 MM patients. Ten patients were remobilized with G-CSF and plerixafor (8 MM patients and 2 lymphoma patients), whereas 19 patients were given plerixafor upfront in the primary mobilization attempt in addition to chemotherapy and G-CSF. The 17 lymphoma patients were followed up after reinfusion of autologous stem cells with regard to short-term and long-term engraftment as well as relapse and death.
The day prior to harvest of the 29 patients, the level of leukocytes was 11.0x109 cells/L (median; range 3.0-40.5), and the CD34+ concentration was 5.5x106/L (median; range 1.9-20.8). Following plerixafor injection, the concentration of CD34+ cells increased to 25.5 x106/L (median; range 5.5-65.6). The patients were then successfully harvested (median: 3.9x106 CD34+cells/kg; range: 1.8-7.2) with 1-2 days of apheresis, although one of the patients only obtained 1.8x106CD34+cells/kg.
In the 17 lymphoma patients receiving high dose therapy followed by autologous stem cell support we observed that time to short-term engraftment, defined by neutrophils >0.5x109/L and thrombocytes >20x109/L were 11 days (median; range 8-19) and 14 days (median; range 10-100) respectively. As an estimate of long-term engraftment we also examined the thrombocyte levels at day 100 after reinfusion. The median level was 135x109/L (range 27-398). Moreover, in contrast to previous findings we have observed durable responses with event free survival of 77% and overall survival of 93% (Median observation time: 24 months). In the MM patients the overall survival observed is 66%.
In conclusion, our findings show that addition of plerixafor is successful in mobilization of hematopoietic stem cells in poorly mobilizing patients resulting in a fast and sustained engraftment as well as equal prognosis for both good mobilizing lymphoma and MM patients after high dose therapy with autologous stem cell support. Our clinical findings therefore justify the extra costs of plerixafor in hard-to-mobilize patients.

Disclosures:
Josefsen: Genzyme: Travel fund 2011 Other.