Abstract

Abstract 33

Background:

Circulating levels of peripheral blood (PB) CD34+ cells/μl are a strong predictor of hematopoietic stem cell (HSC) yields in patients with non-Hodgkin's lymphoma (NHL) undergoing autologous HSC transplantation (auto-HSCT), and are routinely monitored to optimize the timing and success of HSC collection after cytokine ± chemotherapy mobilization. The threshold PB CD34+ cell count to initiate apheresis varies from 5-20 cells/μl, depending on the institution. This analysis compared the efficacy of plerixafor + G-CSF to placebo + G-CSF for HSC mobilization in NHL patients with pre-apheresis PB CD34+ cells/μl <10.

Methods:

Data were obtained from a randomized, double-blind, phase 3 clinical trial comparing the safety and efficacy of plerixafor (0.24 mg/kg/day SC) + G-CSF (10 μg/kg/day) to placebo + G-CSF for mobilization and auto-HSCT in NHL patients. PB CD34+ cell count was measured on Day 4, before the first plerixafor/placebo dose, and on Day 5, 10-11 hours post study drug treatment. The proportion of patients collecting ≥2 × 106 (minimal) or ≥5 × 106 (optimal) CD34+ cells/kg, apheresis yields, and time to engraftment were compared between the plerixafor and placebo groups for patients with PB CD34+ cells/μl <10.

Results:

77/150 (51%) patients and 73/148 (49%) patients in the plerixafor and placebo groups, respectively, had PB CD34+ cells/μl <10 on Day 4, prior to the first dose of study drug. Patient characteristics were similar between both groups. As shown in Table 1, addition of plerixafor to G-CSF resulted in a statistically significant increase in the absolute PB CD34+ cells/μl on Day 5 compared to G-CSF alone (p<0.001). The median fold increase in PB CD34+ cells from Day 4 to Day 5 was significantly higher in plerixafor-treated patients vs. placebo-treated patients: 6.0-fold vs. 1.6-fold (p<0.001). In these hard to mobilize patients, the median CD34+ cell yield after 2 days was significantly higher with plerixafor + G-CSF compared to placebo + G-CSF: 2.92 vs.0.94 × 106 cells/kg (p<0.001), respectively. The median CD34+ cell yield after 4 days was also significantly higher in the plerixafor vs. placebo groups: 3.96 vs.1.25 × 106 cells/kg (p<0.001). Plerixafor + G-CSF allowed a significantly greater proportion of patients with PB CD34+ cells/μl <10 to collect the minimal cell dose in 4 apheresis days: 77.9% vs. 34.2 % patients in the plerixafor and placebo group, respectively collected ≥2 × 106 CD34+ cells/kg in 4 days (p<0.001). The success rate of collecting the ≥5 × 106 CD34+ cells/kg in 4 days was 40.3% with plerixafor + G-CSF compared to only 9.6% with placebo + G-CSF (p<0.001). The proportion of patients collecting the optimal or minimal cell dose in 2 days was also significantly higher in the plerixafor vs. placebo group (p<0.001). The median time to platelet (19-21 days) and neutrophil (10-11 days) engraftment was similar in both groups. Similar, statistically significant increases in PB CD34+ cell collections were obtained when the efficacy of plerixafor + G-CSF was compared to placebo + G-CSF, in patients with a Day 4 PB CD34 cells/μl<20 (data not shown).

Table 1:

Mobilization efficacy

 Plerixafor + G-CSF n=77 Placebo + G-CSF n=73 P-Value 
Day 5 Absolute PB CD34+ cells/μl * 21.71 (0.46-126.4) 5.80 (0-28) <0.001 
Fold Increase in PB CD34+ cells/μl *# 1.6 <0.001 
Cumulative CD34+ cells/kg x 106 after 2 apheresis days* 2.92 (0.03-29.22) 0.94 (0.06-9.16) <0.001 
Cumulative CD34+ cells/kg x 106 after 4 apheresis days* 3.96 (0.03-29.22) 1.25 (0.06-10.58) <0.001 
% Patients achieving ≥2 × 106 CD34+ Cells/Kg in 4 days 77.9 34.2 <0.001 
% Patients achieving ≥5 × 106 CD34+ Cells/Kg in 4 days 40.3 9.6 <0.001 
% Patients achieving ≥2 × 106 CD34+ Cells/Kg in 2 days 67.5 21.9 <0.001 
% Patients achieving ≥5 × 106 CD34+ Cells/Kg in 2 days 23.4 4.1 <0.001 
 Plerixafor + G-CSF n=77 Placebo + G-CSF n=73 P-Value 
Day 5 Absolute PB CD34+ cells/μl * 21.71 (0.46-126.4) 5.80 (0-28) <0.001 
Fold Increase in PB CD34+ cells/μl *# 1.6 <0.001 
Cumulative CD34+ cells/kg x 106 after 2 apheresis days* 2.92 (0.03-29.22) 0.94 (0.06-9.16) <0.001 
Cumulative CD34+ cells/kg x 106 after 4 apheresis days* 3.96 (0.03-29.22) 1.25 (0.06-10.58) <0.001 
% Patients achieving ≥2 × 106 CD34+ Cells/Kg in 4 days 77.9 34.2 <0.001 
% Patients achieving ≥5 × 106 CD34+ Cells/Kg in 4 days 40.3 9.6 <0.001 
% Patients achieving ≥2 × 106 CD34+ Cells/Kg in 2 days 67.5 21.9 <0.001 
% Patients achieving ≥5 × 106 CD34+ Cells/Kg in 2 days 23.4 4.1 <0.001 
*

Values represent Median (Range)

#

Expressed as a ratio of the pre-G-CSF CD34+ cells/μL on Day 5 to pre-G-CSF CD34+ cells/μL on Day 4

Conclusions:

Plerixafor + G-CSF allowed collection of the minimal transplantable cell dose in 78% patients with PB CD34+ cells/μl <10. These data show that adding plerixafor to G-CSF substantially reduces the risk of mobilization failure in patients with NHL predicted to be poor mobilizers based on low PB CD34+ cell counts. Thus, mobilization with plerixafor + G-CSF in patients with PB CD34+ cells/μl <10 increases stem cell collection efficiency allowing patients to pursue auto-HSCT with more optimal cell doses.

Disclosures:

Maziarz:Genzyme Corp.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Micallef:Genzyme Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Stiff:Genzyme Corp.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Bolwell:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marulkar:Genzyme Corporation: Employment, Equity Ownership. Calandra:Genzyme Corporation: Consultancy, Equity Ownership. DiPersio:Genzyme Corporation: Honoraria.

Author notes

*

Asterisk with author names denotes non-ASH members.