Operationalizing SubQ Immune Checkpoint Inhibitors in Clinical Practice

Operationalizing Subcutaneous Checkpoint Inhibitors in Practice

Implementing subcutaneous checkpoint inhibitors requires navigating multiple financial and operational considerations beyond clinical efficacy. New drug launches initially receive temporary J-codes for 6 months, creating reimbursement tracking challenges and potential delayed payments that affect institutional cash flow. Unlike new therapies with superior safety or efficacy profiles that warrant immediate adoption, subcutaneous checkpoint inhibitors offer primarily patient convenience without clinical advantages over IV formulations, reducing urgency for rapid implementation. This contrasts with products such as subcutaneous daratumumab, which demonstrated reduced hypersensitivity and infusion-related reactions, providing clear clinical rationale for adoption. Large practices may strategically delay full implementation until permanent J-codes establish stable average sales price–based reimbursement models.

Economic considerations significantly influence adoption strategies because immunotherapy (IO) represents the largest revenue source for most cancer centers. Pembrolizumab remains the No. 1 IV drug expenditure regardless of institution type (340B, group purchasing organization participation status), with over 40 FDA-approved indications driving widespread utilization. Institutions must ensure that transitioning from IV to subcutaneous formulations does not adversely affect existing pharmaceutical contracts or organizational revenue streams. Current practice models favor physician-centric or advanced practice provider–centric prescribing decisions, allowing providers to convert appropriate patients (eg, those completing combination chemotherapy transitioning to maintenance IO) to subcutaneous formulations based on individual assessment. Automatic substitution policies have not been widely adopted for immunotherapy, contrasting with biosimilar substitution practices in other therapeutic areas, as institutions await greater clarity on evolving market dynamics.

The Inflation Reduction Act (IRA)’s 2028 implementation for IV therapies introduces additional uncertainty into long-term planning. High-cost IV therapies such as pembrolizumab may face significant pricing impacts under IRA provisions, though subcutaneous formulations may fall outside these regulations. Simultaneously, 2028 marks anticipated biosimilar entry for major checkpoint inhibitors. Biosimilars will likely be IV formulations, potentially creating conflicting pressures: Institutions seeking cost reduction or responding to payer mandates favoring biosimilars may need to shift patients back to IV administration, negating patient convenience and quality-of-life benefits achieved with subcutaneous formulations. Patent life extensions through subcutaneous formulation development may delay biosimilar competition but cannot prevent it indefinitely. This dynamic landscape argues against wholesale immediate conversion to subcutaneous products, favoring measured adoption that maintains flexibility to respond to future biosimilar availability, payer mandates, and reimbursement changes while preserving patient-centered benefits for appropriate candidates who would particularly benefit from avoiding IV access challenges.