Introduction. Trilaciclib (Cosela TM), a first-in-class breakthrough therapy, is a novel kinase CDK4/6 inhibitor that protects multiple hematopoietic lineages simultaneously by transiently arresting hematopoietic stem and progenitor cells (HSPC) in the G1 phase of the cell cycle and thus protecting HSPCs from damage by cytotoxic chemotherapy. Administered intravenously prior to the start of chemotherapy, it proactively delivers multilineage myeloprotection and therefore has the potential to improve the 3 major clinical manifestations of chemotherapy-induced myelosuppression (CIM): neutropenia, anemia, and thrombocytopenia. Trilaciclib was approved by the FDA in February 2021 and included in the NCCN Guidelines® in March 2021 for managing CIM in patients with extensive-stage small cell lung cancer (ES-SCLC) treated with a platinum/etoposide-containing or topotecan-containing regimen. As an alternative to single lineage-specific interventions with biological agents for neutropenia ([peg]filgrastim, ), anemia ([darb]epoetin alfa, alfa), and thrombocytopenia (romiplostim), trilaciclib may offer economic value in the prophylaxis and/or management of these adverse events. Cost-efficiency analysis evaluates the costs of various scenarios of delivering treatments to identify the most efficient cost-structure contributing to the value equation. The objective of this cost-efficiency analysis was to determine the savings (losses) in drug costs of managing 1 patient at risk for concurrent neutropenia and anemia and thrombocytopenia (NAT), neutropenia and anemia (NA), neutropenia and thrombocytopenia (NT), or anemia and thrombocytopenia (AT) with trilaciclib as opposed to any combination of biologicals, including biosimilars.Methods. Drug cost inputs included the wholesale acquisition cost (WAC; per REDBOOK; all agents) and the average sales price (ASP; per Centers for Medicare and Medicaid Services; all agents except trilaciclib as no ASP is available yet). An average cost was calculated for biosimilars. Dosing schedules were based on the maximum possible dose therapy in the NCCN Guidelines®. An Excel model was developed to calculate, for the 4 scenarios of CIM and the 32 WAC and ASP cost inputs across all agents, the drug cost for every possible combination of originator and biosimilar agents for 1 patient. These estimates were compared to the WAC of trilaciclib to determine the differential cost-efficiency of trilaciclib in terms of savings ($) accrued or losses (-$) incurred. This analysis focused on treatment with biological agents recommended in the NCCN Guidelines®. It did not consider platelet and red blood cell transfusion for thrombocytopenia and hence is limited to patients for whom transfusion is contra-indicated, physician decision to use romiplostim, or patient preference.Results. Table 1 presents the lowest, highest, mean, and median WAC and ASP differentials by chemotherapy-induced myelosuppression scenario. Mean and median differentials indicated cost savings with trilaciclib use across all chemotherapy-induced myelosuppression scenarios, with the exception of the ASP (with trilaciclib WAC) NA scenarios where losses were noted. Depending on single agents needed, savings ranged from $485.57 (AT ASP) to $9,531.60 (NAT WAC) per patient; with mean/median savings ranging from $646.36/$533.81 (AT ASP) to $7,397.69/$7,358.31 per patient.Conclusions. Myeloprotection with trilaciclib is a cost-efficient intervention when compared to managing individual or multiple myelosuppressive events with single-lineage, supportive care therapies. Unsurprisingly, costing conclusions are affected by the selection of an appropriate price benchmark. ASP tends to fluctuate more than WAC and is typically lower hence an ASP-based cost model may likely underrepresent the cost-efficiency of trilaciclib, as may be the case in the neutropenia/anemia scenario.(Data will be updated by conference time with the trilaciclib ASP if available). [Display omitted] DisclosuresMcBride: BMS: Current Employment. Henry: CVS Health: Current Employment. MacDonald: Matrix45, LLC: Current holder of individual stocks in a privately-held company. Abraham: Matrix45, LLC: Current holder of individual stocks in a privately-held company. OffLabel Disclosure:This presentation will discuss the use of romiplostim for the management of chemotherapy induced thrombocytopenia, an indication for which it has not received FDA approval.