Operationalizing Subcutaneous Immune Checkpoint Inhibitors in Clinical Practice

Implementing subcutaneous immune checkpoint inhibitors in clinical practice requires navigating multiple operational considerations beyond clinical equivalency. Initial implementation challenges include temporary J-codes during the first 6 months post approval that impact reimbursement tracking and may cause delayed payment. Unlike some oncology drug approvals where immediate clinical advantages (such as improved safety with daratumumab subcutaneous reducing hypersensitivity reactions) drive rapid adoption despite reimbursement uncertainties, subcutaneous immune checkpoint inhibitors primarily offer convenience benefits rather than superior efficacy or safety, allowing institutions to strategically time implementation after permanent J-codes establish stable reimbursement models.

Economic considerations extend beyond individual drug reimbursement to institutional revenue management, as immunotherapy represents the largest intravenous (IV) drug expenditure for cancer centers nationwide. Pembrolizumab alone, with over 40 indications, constitutes the No. 1 spending category regardless of whether institutions participate in 340B programs or group purchasing organizations. Health care systems must ensure that transitioning from IV to subcutaneous formulations does not adversely impact existing pharmaceutical contracts or overall organizational revenue streams. Some institutions adopt provider-centric or advanced practice provider–centric prescribing models, allowing individual clinicians to convert appropriate patients (particularly those on maintenance immunotherapy or adjuvant treatment without combination chemotherapy) rather than implementing automatic substitution protocols.

Future considerations include the Inflation Reduction Act’s 2028 impact on IV therapies and the anticipated arrival of biosimilar immune checkpoint inhibitors around the same time frame. The interaction between subcutaneous formulations potentially extending patent life, payer mandates possibly requiring biosimilar utilization for cost reduction, and the reality that biosimilars will be IV formulations creates complexity for long-term planning. Health care systems implementing electronic medical record updates develop innovative solutions like drop-down menus within existing treatment plans allowing selection between IV and subcutaneous formulations rather than building entirely new order sets for each indication, reducing information technology workload while facilitating adoption.