OBJECTIVES: Innovative, branded doublet combination therapies are established in oncology. With more on the horizon, and triplets expected in the near future, combination therapies in oncology may challenge the sustainability of healthcare systems. New approaches to manage drug price and overall budget impact are under discussion by national HTA bodies, as well as the European Federation of Pharmaceutical Industries and Associations (EFPIA). The objective of this analysis is to understand the current and future pricing landscape for innovative, branded combination therapies. METHODS: To understand national P&MA stakeholders’ intended approach to combination therapy pricing, we deep-dive into existing policies and frameworks, upcoming legislation, and position papers. Markets in focus are EU-5, and other countries piloting interesting approaches to combination therapy pricing (e.g., Switzerland, Belgium). To understand recent trends in combination pricing, we conducted a comprehensive assessment of combination therapies recently launched in multiple myeloma – including carfilzomib, daratumumab and elotuzumab in combination with lenalidomide (and dexamethasone), and bortezomib and daratumumab. RESULTS: The analysis indicates payers have already adopted approaches to address higher monthly cost and longer duration of treatment of combination therapies. It also identifies the key drivers of combination therapy P&MA. In many countries, these are aligned with those used to manage budget impact of high-cost oncology monotherapies. CONCLUSIONS: P&MA outcomes are typically the consequence of a combination of factors and are rarely driven by a single factor only. Key drivers of payer management of combination therapy pricing include regulatory label updates, availability of comparative clinical data vs. standard of care, price benchmarks at the time of the HTA assessment, and clinical outcomes. In future, payers are likely to implement further tools to manage combination therapy budget impact, such as innovative outcomes agreements, net price agreements and indication-specific pricing.