Efficacy and Risk Factors Analysis of Upfront Autologous Stem Cell Mobilization Using Plerixafor and Granulocyte-Colony Stimulating Factor (GCSF) in Patients with Multiple Myeloma

Background: G-CSF with or without cyclophosphamide has been commonly used in multiple myeloma (MM) for stem cell (SC) collection prior to autologous stem cell transplantation (ASCT). Several risk factors including age, prolonged exposure to lenalidomide, and low platelet count are associated with suboptimal stem cell harvest. Plerixafor selectively and reversibly binds to the chemokine receptor CXCR4 and blocks its interaction with stromal cell-derived factor-1α. This drug was approved by the FDA for stem cell mobilization in MM, based on phase III studies demonstrating the superiority of plerixafor and G-CSF over G-CSF alone in achieving a predetermined target yield of 6 × 10⁶CD34+ cells/kg collected in < 2 phereses; however, this outcome is not clinically relevant. The purpose of this retrospective study is to examine the SC mobilization efficiency associated with plerixafor using a more clinically relevant outcome, and to identify risk factors associated with poor SC mobilization, including the potential impact of prior exposure to lenalidomide-containing regimens.

Patients and methods: This retrospective study examined MM patients mobilized with plerixafor and G-CSF upfront as part of initial therapy at Memorial Sloan Kettering Cancer Center between 4/1/2009 and 8/1/2013. Baseline characteristics examined included age, race, gender, platelet count, WBC count, and marrow plasmacytosis prior to mobilization. Treatment characteristics examined included type of induction regimen (distinguishing regimens containing lenalidomide only, bortezomib only, or both), number of cycles received, time between last chemotherapy and SC mobilization, time between start of treatment and SC collection, and prior radiation. The primary endpoint was the rate of SC collection success, defined as the ability to collect at least 5 x 10⁶CD34+ cells/kg during the first set of phereses, which would be sufficient for two ASCT. The secondary endpoint was SC collection efficiency, measured by the number of CD34+ cells yielded per pheresis performed during the first set of stem cell collection. Linear regression was used to examine the univariate effect of baseline and treatment variables on SC collection efficiency. Variables significant at the 0.05 level were entered into a multivariable model.

Results: A total of 138 MM patients were mobilized with plerixafor and G-CSF before proceeding to stem cell collection. The rate of SC collection success was 92.8%. Due to this high success rate, we could not identify independent risk factors associated with poor SC mobilization. When considering SC efficiency as outcome, the average efficiency for the entire cohort was 7.25 x 10^6 CD34+ cells/kg/pheresis. Increased age (p=0.005), shorter time between treatment start and SC collection (p=0.05), higher number of cycles received during induction treatment (p=0.042), lower platelet count (p=0.009) and lower WBC prior to G-CSF (p=0.01), and exposure to lenalidomide only (p=0.011) were all identified as risk factors by univariate analysis. Only lower WBC prior to GCSF (p=0.009) maintained statistical significance after multivariate analysis.

Conclusions: This retrospective study shows that plerixafor is a highly effective agent for SC mobilization and collection in MM patients, with only few patients failing to achieve the target collection regardless of baseline or treatment characteristics including prior lenalidomide exposure. However, we identified WBC prior to G-CSF administration as a predictor of SC collection efficiency. These results provide strong support to the upfront use of plerixafor and G-CSF for SC mobilization in MM patients. A cost analysis is currently in progress comparing this SC collection modality with other conventional means currently being employed in patients with MM.