Development of Processes to Ensure Timely Administration of Tocilizumab in the Setting of Cytokine Release Syndrome after Administration of Tisagenlecleucel or Axicabtagene Ciloleucel

Abstract

Introduction With the commercial approval of tisagenlecleucel and axicabtagene ciloleucel, tocilizumab was concurrently approved by the Food and Drug Administration (FDA) for the management of cytokine release syndrome (CRS).1,2 Per the FDA Risk Evaluation and Mitigation Strategy (REMS) requirements, the pharmacy must stock a minimum of two doses of tocilizumab for each patient, available for administration within two hours.1,2 The complex logistics of the immediate administration of this product in a large academic medical center required coordination of a multidisciplinary team. Objectives/Methods Our multidisciplinary team participated in weekly meetings to develop standard policies and treatment algorithms to treat the acute toxicities seen with tisagenlecleucel and axicabtagene ciloleucel. We also created an annual pharmacy competency outside of the REMS requirements for all inpatient pharmacy staff to ensure awareness and emphasize the need for prompt administration of tocilizumab. Our IT team worked to develop electronic solutions including a PRN entry of tocilizumab that would be released concurrently with the cell infusion order and would be readily available on the patient's medication administration record (MAR) for immediate dispensing. As CRS can occur following the initial admission, we created a “prepare and give now” entry for tocilizumab within our toxicity treatment order set in preparation of potential future admissions. The entry includes help text with the dosing information and is capped at 800 mg. For all scenarios in which tocilizumab administration is necessary, the attending on service is required to call the inpatient pharmacy directly to provide the verbal order to dispense a dose. This safety step ensures that the attending on service is knowledgeable of the patient's symptoms and agrees with use. Results/Conclusion Of the patients that we have treated to date, our median number of tocilizumab doses is 1 dose (range 0-4). Our median time from dispense to administration is 53.5 minutes (range 23-85 minutes) [Table 1]. This demonstrates that our education efforts and available resources have resulted in our ability to properly manage CRS and to dispense and administer tocilizumab well under the 2-hour time frame dictated by the REMs requirements.