Evaluation of a Risk-Based Algorithm for the Utilization of Plerixafor As Primary Mobilization of CD34+ Cells in Autologous Hematopoietic Cell Transplant Candidates,

Abstract

4060 Study Purpose and Methods: Following FDA approval of plerixafor, our institution developed practice guidelines using a risk-based algorithm to optimize the use of plerixafor for CD34 cell mobilization in autologous hematopoietic cell transplant (HCT) candidates. We defined patients (pts) at high risk for mobilization failure and eligible to receive G-CSF 10 mcg/kg/day for 4 days with plerixafor 0.24 mg/kg added on day 4 if they met any of the following criteria: 1) 3 or more lines of prior chemotherapy; 2) 2 or more lines of prior chemotherapy plus a radioimmunoconjugate or extensive field radiation therapy (XRT); 3) 4 or more cycles of hyper-CVAD, 4) 4 or more cycles of lenalidomide; or 5) hypocellular bone marrow (<25% cellularity) prior to mobilization. Apheresis began on day 5 of mobilization for all pts. Pts not meeting this criteria received G-CSF alone unless the first day apheresis yield was less than 0.5 million CD34 cells/kg or peripheral CD34 count was <10/μmL in which case plerixafor was added. In order to evaluate the efficacy of plerixafor in these high risk patients and validate the risk categories, we conducted a retrospective review of consecutive pts mobilized before and after guideline institution. The primary endpoint was the proportion of pts collecting 2 million CD34 cells/kg in one apheresis. Results: 415 pts were mobilized between 1/1/2008–8/31/10, 334 received G-CSF and 81 received G-CSF and plerixafor. G-CSF pts received 10 or 20 mcg/kg/day for 4 days, depending on institutional practice. This analysis includes those determined to be high risk by the above listed categories: 124 G-CSF pts and 72 plerixafor pts. The most common high risk categories represented were 3 or more lines of prior chemotherapy (group 1): 61 G-CSF pts and 27 plerixafor pts; 4 or more cycles of hyperCVAD (group 2): 14 G-CSF pts and 15 plerixafor pts; and 4 or more cycles of lenalidomide (group 3): 31 G-CSF pts and 27 plerixafor pts. For group 1 patients 38% of G-CSF pts collected >2 million in one apheresis compared to 67% of plerixafor pts (p=0.014). For group 2 pts, the respective proportions were 21% vs 47% (p=0.153) and for group 3 pts, the respective proportions were 39% vs 100% (p<0.001). Conclusions: Our results validate the risk categories used in our guidelines since less than 50% of high risk G-CSF patients analyzed were able to mobilize a sufficient number of CD34 cells with one apheresis. In addition, plerixafor was associated with a larger proportion of pts who collected 2 million CD34 cells/kg in one apheresis, suggesting superior efficacy in these high risk patients. We conclude that there are specific pts that should receive plerixafor in order to reduce the number of aphereses necessary to proceed to HCT. This may be a more reliable and efficient practice than assessing peripheral CD34 counts prior to apheresis as these counts may not always accurately predict CD34 yield or be available in a timely manner. Disclosures: Shapiro: Genzyme: Research Funding, Speakers Bureau. Perkins:Genzyme: Research Funding. Bookout:Genzyme: Research Funding. Fernandez:Genzyme: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Optimizing Autologous Stem Cell Mobilization Strategies to Improve Patient Outcomes: Consensus Guidelines and Recommendations

“…In a phase II trial, the addition of plerixafor to G-CSF mobilization increased rates of successful mobilization (defined as !5 Â 10 6 CD34 þ cells/kg) and was associated with fewer apheresis sessions compared with G-CSF alone [129]. Two subsequent large Phase III trials of upfront plerixafor þ G-CSF (P þ G-CSF) mobilization confirmed that the combination was associated with higher CD34 þ cell yields, better achievement of collection targets, lower failure rates, and fewer apheresis sessions compared with G-CSF alone [66,67,[130][131][132][133].…”

“…Plerixafor also has been used in risk-adapted strategies in which patients with high-risk baseline characteristics are mobilized with P þ G-CSF. One single-center report of P þ G-CSF use in patients at high risk for mobilization failure based on previous chemotherapy regimens showed significantly improved mobilization compared with historical controls who received G-CSF alone [133]. Another retrospective study of P þ G-CSF in patients at high risk for failure based on medical history found a failure rate of only 4%; however, it should be noted that one-third of the patients in this cohort had previously failed mobilization [131].…”

“…This effect may be linked to the duration of lenalidomide exposure, given that stem cell yields may be significantly lower in patients receiving more than 4 to 6 cycles [74,84,152]. Both CM and plerixafor-containing mobilization strategies have been shown to overcome this negative effect and result in successful collections [133,[152][153][154][155][156].…”

“…Their findings may have limited application to other institutions, however, given the differing costs, patient populations, transplantation goals, and mobilization strategies among centers. Without pharmacoeconomic data from a multicenter controlled trial, centers have developed algorithms to guide the use of plerixafor within steady-state G-CSF mobilization based on PB CD34 þ cell counts, daily apheresis yields, and the presence of risk factors for failure [96,98,99,133,138]. In these algorithms, the most common approach requires performing PB CD34 þ cell analysis on day 4 of G-CSF administration; if the count is below a predetermined threshold, then plerixafor is administered on the evening of day 4, and the start of apheresis is delayed until day 5.…”

Pharmacoeconomics of Hematopoietic Stem Cell Mobilization: An Overview of Current Evidence and Gaps in the Literature

“…Plerixafor is indicated for first-line mobilization of hematopoietic stem cells into the peripheral blood for collection and subsequent autologous transplantation in patients with NHL and MM. Several studies, including the initial phase III trials of plerixafor and G-CSF compared with G-CSF and placebo, have demonstrated that plerixafor can overcome some of the known risk factors for poor stem cell mobilization [26,43,[59][60][61], and may reduce overall mobilization failure rates from as high as 30% to <10% [16,21,[62][63][64][65][66][67][68]. Unfortunately, the acquisition cost of plerixafor has limited its use in up-front mobilization despite the FDA indication, as expensive agents within institutions are often restricted because of budget constraints.…”