A Retrospective Evaluation of the Impact of Pre-Emptive Plerixafor Administration on Collection Efficiency in Patients with Myeloma Undergoing Stem Cell Mobilization

Background: High dose melphalan with autologous stem cell support (aSCT) remains one of the most beneficial therapies for myeloma. However, this therapy may be limited by the ability to collect a minimum CD34+ cell dose of 2.0 × 10⁶/kg. Failure to collect an adequate CD34+ cell dose leads to significantly increased costs and treatment delays. Plerixafor (PL) is a mobilization agent which reversibly inhibits binding of SDF-1 to the chemokine receptor CXCR4, resulting in mobilization of hematopoietic progenitor cells. Phase 3 studies demonstrate that administration of PL significantly improves the likelihood of successful CD34+ cell collection compared to G-CSF alone (Dipersio, Blood 2009) in patients with myeloma and NHL. In order to improve collection efficiency, our center began a policy of PL administration to all myeloma patients undergoing collection pre-emptively on the evening prior to Day 1 of collection. Herein we evaluate the outcomes of that policy change when compared to patients who received PL on Day 1 (D1) of collection according to a treatment algorithm which evaluated peripheral blood (PB) CD34+ cell number as well as D1 CD34+ cell dose collection.

Methods: Patients with myeloma undergoing mobilization who received PL during their treatment course were eligible. Patients were categorized according to timing of administration to either pre-emptive (P-PL) or standard (S-PL), which was given according to a treatment algorithm on day 1 of collection based on CD34+ cell dose. Patients were evaluated for total CD34+ dose procured, number of apheresis procedures, risk factors for poor mobilization and collection (age, prior therapies, and DM), and pre-emptive vs. standard PL. A multivariable logistic regression model was built to predict the ability to achieve minimum collection goal.

Results: From 2009 to 2014, 299 patients received PL during stem cell mobilization and were available for evaluation. Of these, 241 received P-PL and 58 received S-PL. There were no significant differences between patient groups with respect to sex, age, race, KPS, ISS score, CMI, # of prior therapies, prior lenalidomide, DM-2, or disease status at the time of transplant. As expected, patients who received P-PL had significantly better collection. Patients who received P-PL had a median CD34+ peripheral blood cell count (absolute) on the day before collection of 21 (range 0-162) vs. 8 for S-PL (range 3-90, p<0.0001). Median total CD34+ cell dose collected on D1 of collection was 6.75 in the P-PL group vs 1.96 in the S-PL group (p<0.0001). There was no significant difference in collection efficiency for days 2 and 3 of collection between the groups. There was no difference between the numbers of doses of PL received, with both groups receiving a median of 1 dose (range 1-3 for both). The majority of P-PL patients completed collection in 1-2 collections (99%) vs. 64% for S-PL (p<0.0001). With respect to engraftment, there were no differences between the groups for platelet engraftment to 20,000/mcl, however patients in the P-PL group had a significantly longer ANC engraftment time (11 vs. 10 days, p<0.0001), possibly explained by a change in post-transplant filgrastim administration to day +7 which occurred during that time; these patients also had a longer hospital stay, possibly for the same reason. On univariable analysis, pre-emptive PL was the only factor significantly associated with likelihood of collection of at least 2.0 x 10⁶ CD34+ cells/kg on first collection (p<0.0001). On multivariable analysis, factors significantly associated with collection of at least 2.0 x 10⁶ CD34+ cells/kg on D1 included P-PL (p<0.0001), CR or PR at the time of collection (p=0.03), and DM-2 (p=0.05). Two patients in the P-PL group failed to collect 2.0 x 10⁶ CD34+ cells/kg by day 4 of collection despite this up-front strategy; the cell doses collected were 1.91 x 10⁶ and 1.99 x 10⁶.

Conclusions: Up-front administration of PL significantly enhances collection efficiency, with the majority of patients (77%) completing collection in one day.