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.

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.

*Data from Delaney.¹

 

Key learnings
Tocilizumab is effective for the treatment of early CRS. After two doses, response times may increase, and alternative therapies such as corticosteroids should be considered in refractory cases.