Monitoring patients for cytokine release syndrome is a key aspect of caring for patients receiving teclistamab.
Closely monitoring patients with multiple myeloma for signs of cytokine release syndrome (CRS), ruling out infection as a diagnosis, and partnering with patients as well as physicians to allow for quick intervention and transfers to intensive care—when necessary—are key to safely caring for patients receiving teclistamab-cqyv (Tecvayli).1
Safety data from the phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098) which were presented by Donna Catamero, ANP-BC, OCN, CCRC, during the 48th Annual Oncology Nursing Society (ONS) Congress, demonstrated that CRS was successfully managed with premedication, step-up dosing (SUD), and prompt diagnosis as well as intervention for patients treated with teclistamab (n = 165).
In MajesTEC-1, 72.1% (n = 119) of patients experienced CRS. All events were grade 1 or 2, save for 1 patient who experienced a grade 3 event in an infection setting. Grade 1 and 2 events were reported in 50.3% and 21.2% or patients, respectively. The median time to CRS onset was 2 days (range, 1-6) with a CRS median duration of 2 days (range, 1-9). There were no recurrent cases reported.
Conditions such as infections can present with similar symptoms as CRS, therefore, early assessment at onset of fever may help nurses distinguish CRS from infections. It is advised that all infections be resolved before beginning treatment with teclistamab as infections may exacerbate CRS.
CRS management strategies were chosen in accordance with CRS severity and institutional guidelines. Supportive measures included tocilizumab (Actemra; 36.4%), intravenous fluids (13.9%), low-flow oxygen (12.7%), steroids (8.5%), single vasopressor (0.6%), and other (61.2%). Patients were able to receive more than 1 supportive measure. Tocilizumab as an intervention could be considered for grade 1 CRS and was recommended for CRS occurring at grade 2 or higher.
Of note, according to study authors, almost all patients who experienced a CRS event did so during SUD and all first CRS events occurred before the end of cycle 1. These findings highlight the importance of frequent monitoring and extra vigilance during this time period, they said.
“In our experience the real-world supportive care measures for CRS align with those outlined in the MajesTEC-1 study protocol and with the teclistamab prescribing information. We frequently gave tocilizumab with grade 1 CRS—especially in cases where there was no improvement with symptomatic treatment,” Catamero, who is associate director of Myeloma Research at Mount Sinai, wrote in the poster.
“Both formal guidelines and practical guidance are needed for nurses to monitor for CRS, recognize it, and promptly intervene in order to ensure a safe administration of teclistamab,” she added.
CRS is a systemic inflammatory response associated with T-cell engaging-bispecific antibodies, such as teclistamab. In October 2022, the FDA granted teclistamab accelerated approval for adult patients with relapsed or refractory multiple myeloma.2 Because nurses are on the front line of patient care, their ability to recognize and respond to CRS is critical in helping patients safely receive this medication.
As part of the MajesTEC-1 study, a SUD schedule was used to reduce the risk of high-grade CRS. Patients were also premedicated with a corticosteroid, histamine-1 receptor antagonist, and antipyretic. Doses were as follows: on day 1, day 4, day 7, and day 14 of the study, patients received 0.06 mg/kg, 0.3 mg/kg, 1.5 mg/kg, and 1.5 mg/kg once weekly, respectively. After day 14, patients continued to receive 1.5 mg/kg weekly for all subsequent doses.1
Vitals were monitored before each teclistamab dose and 4 to 6 times a day. Every 2 to 4 hours, the inpatient nursing team assessed temperature, respiration, O2 saturation, neurologic assessment, blood pressure, heart rate, and cardiac monitoring. Any other symptoms were discussed as needed (shivering, pain, rash, difficulty breathing, etc.)1
The American Society for Transplantation and Cellular Therapy Criteria was used to grade CRS and the immune effector cell encephalopathy questionnaire was used in addition to handwriting assessments to monitor for possible neurotoxicity. A risk evaluation and mitigation strategy program was used to assist in training nurses to recognize CRS in addition to in-services, online modules, clinical lessons, and posters/leaflets which are also tools utilized in the monitoring and managing CRS. Patients were also educated on CRS as a potential adverse event.1
Physicians were consulted once daily or more depending on necessity. Nurses were instructed to immediately consult a physician if patients had signs of infection, a temperature of 38 °C or more, a drop in blood pressure or O2 saturation, experienced pains or chills, and if signs of neurotoxicity were present.
Editor’s Note: This study was funded by Janssen Research & Development. The principal study author has received payment from GSK, BMS, and Janssen.