Background: Biosimilars have the potential to reduce the cost of prophylaxis of CIN/FN. To demonstrate this, we: 1) conducted a US comparative cost-efficiency analysis of CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv over reference pegfilgrastim without or with on-body injector (PEG/PEG-OBI), 2) modeled budget-neutral expanded access to biosimilar pegfilgrastim-cbqv from cost-savings achieved from conversion from PEG/PEG-OBI, and 3) estimated the number-needed-to-convert (NNC) to biosimilar pegfilgrastim-cbqv from PEG/PEG-OBI to purchase one additional treatment of biosimilar pegfilgrastim-cbqv. Methods: Simulation modeling from the US payer perspective utilizing: average selling price (ASP) derived from CMS Q1 2020 reimbursement limits for PEG/PEG-OBI and pegfilgrastim-cbqv;between one and six cycles of prophylaxis in a panel of 20,000 cancer patients at risk for CIN/FN; and conversion rates from PEG/PEG-OBI to biosimilar pegfilgrastim-cbqv ranging from 10% to 100% in this panel. Results: Using current ASP, cost-savings per patient of biosimilar pegfilgrastim-cbqv over PEG/PEG-OBI ranged from $223 (for 1 cycle) to $1,335 (6 cycles). In a panel of 20,000 cancer patients, the savings range from $445,163 (for one cycle of prophylaxis at 10% conversion) to $26,709,788 (6 cycles at 100% conversion). In a single cycle of chemotherapy, these savings translate into expanded access to prophylaxis with biosimilar pegfilgrastim-cbqv ranging from 115 doses at 10% conversion from PEG/PEG-OBI to 1,154 doses at 100% conversion. The savings over six cycles of chemotherapy could provide between 692 additional doses of biosimilar pegfilgrastim-cbqv prophylaxis (at 10% conversion) to 6,921 doses (at 100% conversion). The NNC from PEG/PEG-OBI to purchase one additional dose of biosimilar pegfilgrastim-cbqv is 18. Conclusions: These models demonstrate that CIN/FN prophylaxis with biosimilar pegfilgrastim-cbqv can generate significant cost savings that could be reallocated on a budget-neutral basis to provide more patients and/or more cycles with CIN/FN prophylaxis.