Tocilizumab for the management of cytokine release syndrome: Real-world data

Tocilizumab, an interleukin-6 inhibitor, is indicated for the treatment of chimeric antigen receptor (CAR) T-cell-associated cytokine release syndrome (CRS).¹ During the European Society for Blood and Marrow Transplantation-European Hematology Association (EBMT-EHA) 6th European CAR T-cell meeting, Delaney¹ presented real-world data on the use of tocilizumab for the management of CAR T-cell-associated CRS; we have summarized the presentation below.

Methods

• This analysis included 10 patients who received CAR T-cell therapy at the Sheffield Teaching Hospitals NHS Foundation Trust.
  • Six patients with large B-cell lymphoma received axicabtagene ciloleucel, and four patients with mantel cell lymphoma received brexucabragene autoleucel.
• Tocilizumab treatment for CRS is shown in Figure 1.
• Time to response was defined as the time for a patient to drop ≥1 CRS grade.
  • Grade 1 CRS was defined as the time for the patient’s temperature to return to normal.
  • Grade 2 CRS was defined as the time for the patient’s blood pressure to return to normal without needing fluid support or for their oxygen saturation to return to >94% without supplemental oxygen.
  • Patients with Grade ≥3 CRS were not included in the response time analysis.

Figure 1. Sheffield Teaching Hospitals reference guide to CRS management* 

CRS, cytokine release syndrome; ICU, intensive care unit; IV, intravenously.
Adapted from Delaney.¹

Key findings

• In total, nine patients developed CRS:
  • Median day of CRS onset was Day 1 (range, 1–8);
  • Average CRS duration was 5.5 days (range, 1–8.5); and
  • Median day of maximum CRS was Day 4 (range, 1–8).
• Three patients developed Grade 3 CRS requiring vasopressors, of which two were aged >70 years, and two developed Grade 3 immune effector cell-associated neurotoxicity syndrome.
• Two patients received one dose, two received two doses, three received three doses, and two received four doses of tocilizumab.
• Median administration of the first tocilizumab dose was on Day 2 (range, 1–9).
• Average response times were similar between the first and second tocilizumab doses but increased with further doses (Figure 2).
  • Response times were faster for Grade 2 vs Grade 1 after the first and second doses; however, additional resuscitative measures were also given (Figure 2).
• Of the two patients who received their first tocilizumab dose for Grade 1 CRS at 24 hours, response time was relatively long at 11 and 15 hours, respectively, and this did not prevent higher grade CRS or needing further tocilizumab doses.

Figure 2. Average tocilizumab response time*

*Data from Delaney.¹