Effectiveness and Potential Strategies to Improve Outcomes Following Chemomobilization with Etoposide + G-CSF in Patients Undergoing Autologous Stem Cell Transplantation for Lymphoma

The addition of chemotherapy to G-CSF for stem cell mobilization prior to autologous stem cell transplantation (ASCT) provides the potential for increased cell yield and improved mobilization outcomes relative to G-CSF alone. We have investigated the use of mid-dose VP-16 plus G-CSF in pts with lymphoma and examined whether plerixafor might be incorporated into this chemomobilization backbone in a cost-effective way for a population with inferior outcomes. METHODS: Between June 2004 and September 2010, 159 pts with lymphoma underwent ASCT following the use of VP-16 (375mg/m² on D#1 and D#2) and G-CSF (5mcg/kg twice daily from D#3 through the final day of collection) for mobilization. 26 pts also received a dose of Rituximab (375mg/m²) on D#1. Stem cell collection was initiated when the peripheral blood CD34 cell count was more than 7 per ul. Data on costs for fixed and variable expenditures associated with mobilization and collection were calculated on an individual patient basis. Costs also included unexpected complications such as inpatient hospitalizations, antibiotic use and blood product transfusions. “Poor mobilizers” were defined as pts failing to collect 5 × 10⁶ cells in one or two days. Univariable and multivariate logistic regression were performed to identify predictive models for poor mobilization and to identify hypothetical breakpoint scenarios for the cost-effective utilization of plerixafor. For the breakpoint scenarios, a median of 3 doses of plerixafor was assumed based on the published phase III data with plerixafor plus G-CSF. RESULTS: Of 159 pts with lymphoma, 90 (57%) were identified as “good mobilizers,” 43% were “poor mobilizers”, and 150 (94%) collected at least 2 × 10 6^th/kg CD34 cells in total (83% within 4 apheresis sessions), comparing favorably to published data with G-CSF alone or G-CSF + plerixafor. 51 (32%) required PRBC or platelet transfusion, 10 (6%) were admitted to the hospital during the mobilization period, and 8(5%) required a second mobilization or bone marrow harvest. There was no increased incidence of secondary malignancies. Average costs were $14923 ($6121-$24546) for good mobilizers and $27044 ($12206-$51846) for poor mobilizers (p<0.05). The first peripheral blood CD34 count (obtained between D9-D15, with 82% of first counts obtained on D12), accurately predicted “good” vs “poor” mobilizers (c statistic 0.941, CD34 cutpoint 27/uL). Using our data, we estimated that it would not be cost effective to give plerixafor to all patients, even if 100% of patients subsequently became “good” mobilizers (net loss $15,817/pt). Instead, by reserving plerixafor for only predicted “poor” mobilizers (probability<0.5) at the time of first CD34 count, we estimated that 64% (n=49) of predicted “poor” mobilizers would need to become “good” mobilizers in order to achieve cost neutrality. CONCLUSION: VP-16 and G-CSF is a safe and effective mobilization regimen for pts with lymphoma and compares favorably to published data with G-CSF alone or G-CSF + plerixafor. Mobilization outcomes after chemomobilization might be further improved in a cost-effective way by adding plerixafor in patients predicted by the first peripheral blood CD34 count to be poor mobilizers. This will be investigated prospectively.

Shea:Otsuka Pharmaceuticals: Research Funding.