Physicians Develop Guidelines to Manage CAR T-Cell Toxicity

Cytokine release syndrome (CRS) and chimeric antigen receptor (CAR) T cell—related encephalopathy syndrome (CRES) are significant side effects that are not commonly encountered when patients are treated with anticancer agents; however, these are a common phenomenon among patients treated with CAR T-cell therapies. Now, physicians across different institutes who have been involved in clinical trials of CAR T cells in B-cell lymphomas have developed a guideline for managing CRS and CRES.

The review is based on the experiences gained when treating over 100 patients who received care at MD Anderson Cancer Center at the University of Texas, Moffitt Cancer Center in Tampa, Sylvester Cancer Center at the University of Miami, and Mayo Clinic Cancer Center in Rochester, Minneapolis.

Following is an overview of some of the recommendations:

• The onset of CRS occurs within the first week after CAR T-cell therapy and peaks within 1 to 2 weeks of cell administration. Monitor for at least 7 days after CAR T-cell infusion: vital signs every 4 hours, daily review of organ systems, physical exam, complete blood count, complete metabolic profile, coagulation profile, measurement of serum C-reactive protein
• Temperature needs monitoring Patients who develop fever should be assessed for infection In patients who have an infection prior to treatment, CAR T-cell infusion should be delayed till the infection is controlled
• Cardiac monitoring is advised, due to a high risk of arrhythmias
• Other organs to be monitored include the respiratory tract, gastrointestinal tract, liver, kidneys, among others
• Recommendations on supportive care prior to the infusion include, but are not limited to: Baseline brain magnetic resonance imaging Cardiac monitoring Seizure prophylaxis Tumor lysis precautions in patients with bulky tumors
• Close monitoring of patient’s blood pressure, heart rate, and respiratory rate
• Blood and urine cultures for patients with a temperature of 38.3° C or higher

The authors have also developed a 3-step flowchart for easier assessment and management of acute toxicities with this treatment, as well as concise tables for identifying and managing different grades of CRS and CRES.

“This represents a sea change in how we treat these patients,” said lead author Sattva Neelapu, MD, professor of Lymphoma and Multiple Myeloma at MD Anderson, in a statement. “There have been no new treatments approved for patients with aggressive B-cell lymphomas relapsing after first line therapy in 30 years, and only about 10% survive long term.”

Highlighting that CAR T-cell infusions are potentially curative, Nellapu added, “The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly.”

Reference

Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2017. doi: 10.1038/nrclinonc.2017.148.