Cytokine release syndrome is a possible complication of CAR-T cell infusions. Patients who develop cytokine release syndrome (CRS) present with symptoms of fever, nausea/vomiting, fatigue, headache, confusion and/or myalgias. Up to 1/3rd of patients will develop profound hypotension, liver and/or kidney dysfunction, and/or oxygen requirement these patients need ICU care. CRS is IL-6 driven and can be effectively treated with anti-IL6 antibody therapy (tocilizumab) which is FDA approved and on-site.
A CRS management team has been formed and consists of Drs. Levine, Jagannath, Madduri, Osman, Richter, Steinberg and Malone. One of these physicians will be available 24/7 and must be involved in CRS management. CRS ATTENDING ON CALL is listed in AMION.
KEY POINTS FOR COVERING PROVIDERS FOLLOWING CAR-T CELL INFUSION:
1. DO NOT GIVE STEROIDS WITHOUT FIRST CHECKING WITH THE COVERING CRS PHYSICIAN. The gene modified T-cells are as sensitive to steroids as any other T-cell. As a result, steroids can wipe out the therapeutic cells, leaving the patient in their original state high risk heme malignancy. The management of CRS is a steadily escalating protocol where tocilizumab is only given if the patient requires high dose vasopressors, high flow O2, or rapid clinical deterioration. Steroids are only given if tocilizumab is ineffective. Stress dose steroids are to be avoided as well.
2. DO NOT GIVE TOCILIZUMAB WITHOUT FIRST CHECKING WITH THE COVERING CRS PHYSICIAN. Tocilizumab may shut down the proliferation of T-cells required to control the malignancy, so we plan to hold off on giving this agent unless supportive care is unable to stabilize the patient.
3. GIVE ANTIBIOTICS, SUPPORTIVE CARE, ETC PROMPTLY FOR PATIENTS WITH PRESUMED CRS, BUT WHO MIGHT ACTUALLY BE INFECTED. NOTIFY THE COVERING CRS PHYSICIAN OF ANY SYMPTOMS. Not all fever is CRS, so we need to treat these patients with central lines the same as any other highly immunocompromised oncology patient. All will have received chemo shortly before infusion.
4. THE STUDY PI WILL NOTIFY THE ED IF THE PATIENT IS BEING REFERRED TO THE ED.
5. OUTPATIENTS WITH FEVER AFTER CAR-T CELL INFUSION SHOULD BE ADMITTED TO 11C IF OTHERWISE WELL AND HEMODYNAMICALLY STABLE. Fever is the primary presenting symptom of CRS and more severe symptoms are not expected for another 1-5 days after initial fever. Prompt admission is desired. Antibiotics should be given per routine for patients with central lines who are not neutropenic. If any patients are directed to the ED, please reinforce with the ED the above guidelines, in particular NO STEROIDS.