Efficacy
In the two phase III randomized trials, 298 patients with NHLr and 302 with MMr were recruited. In the NHL group, the primary endpoint (>5 x 106 CD34+ cells/kg) was reached in 59% of the plerixafor-treated patients and 20% of those who received placebo (P<0.001). In the plerixafor group, 86.7% obtained at least 2 x 106 CD34+ cells/kg, compared to 47.3% in the placebo group, which is considered the minimum requirement to safely proceed to autologous transplant (P<0.001).
Results were similar in the MM study, where the primary endpoint (>6 x 106 CD34+ cells/kg) was reached in 71.6% in the plerixafor group and 34.4% in the placebo group (P<0.001). Comparing between groups for the achievement of at least 2 x 106 CD34+ cells/kg, this was also higher in patients given plerixafor at 95.3% versus 88.3% (P=.031). Fifty-four percent of patients met the primary endpoint after one apheresis following plerixafor, while 56% of patients receiving placebo required four apheresis sessions to reach this target.
Long term follow-up of patients included in the 2 phase III randomized trials has been published.r There were no significant differences in terms of progression-free or overall survival in patients treated with plerixafor or placebo.
The results of compassionate access studies from Europe and the US have shown the efficacy of plerixafor in patients who had failed mobilisation and were therefore not eligible for the registration trials.rrrr Using the same combined G-CSF and plerixafor protocol, between 40-75% of patients were able to achieve collection of at least 2 x106/kg CD34+ cells.
A Cochrane review of published trials of plerixafor for haematopoietic stem cell mobilization concluded that the addition of plerixafor leads to increased stem cell collection in a shorter time.r
Study |
Patient population |
Patient number |
Achieved ≥2x106 CD34+ cells/kg |
2009 DiPersior |
Phase III: NHL first mobilisation |
Plerixafor: 150
Placebo: 148
|
Plerixafor: 86.7%
Placebo: 47.3%
P<0.001 |
2009 DiPersior |
Phase III: Myeloma first mobilisation |
Plerixafor: 148
Placebo: 154
|
Plerixafor: 95.3%
Placebo: 88.3%
P=0.031 |
2008 Calandrar |
US compassionate use data for failed mobilisation
|
NHL: 63
MM: 35
HL: 17
|
All: 66.1%
NHL: 60.3%
MM: 71.4%
HL: 76.5%
|
2011 Duarter |
EU compassionate use data for failed mobilisation
|
NHL: 22
MM: 32
HL: 2 |
All: 75%
NHL: 63%
MM: 84% |
2009 Micallefr |
Salvage in patients with failed mobilisation from Phase III NHL trial (DiPersio2) |
Prior plerixafor: 11
Prior placebo: 57 |
Prior plerixafor:40%
Prior placebo:63% |
2012 Malardr |
EU compassionate use data for failed mobilisation after previous fludarabine or lenalidomide |
Prior fludarabine: 48
Prior lenalidomide: 35 |
Prior fludarabine:58%
Prior lenalidomide:69% |
Plerixafor has also been used in a pre-emptive or ‘on demand’ fashion to increase the likelihood of patients at risk of failing stem cell mobilisation using chemotherapy and/or G-CSF.rrrr With these strategies 13/16 (81%),r 33/34 (97%)r and 98/102(96%)r of patients were able to meet cell collection targets.