Table 1.

Therapeutic approaches for CAR T-cell therapy–related neurotoxicity

Therapy	Timing	Comments
IV corticosteroids	Therapeutic14, 15, 16	Among patients who received corticosteroids at the onset of grade 3 (ZUMA-1 C 1+2) and earlier for grade 1 NEs (C4), rates of grade ≥3 NEs were 28% and 17%, respectively.
IV corticosteroids	Prophylactic28,29	The incidence of grade ≥3 NEs in ZUMA-1 C6 (13%) was comparable to that of C4 (17%), and both rates were comparably lower than C1+2 (28%). In ZUMA-1 C6, patients received once-daily oral dexamethasone at 10 mg plus C4 management on d 0 (before axi-cel), 1, and 2. The updated follow-up included a few additional NEs and the total incidence of grade ≥3 NEs was 15%.
Anakinra	Therapeutic30, 31, 32	Four of 6 patients who received anakinra for the management of high-grade ICANS experienced clinical benefit.32 In 9 out of additional 14 patients with ICANS, the reduction of peak ICANS could be reached within 1 day after the last anakinra dose.30 Twenty three patients treated with anakinra for steroid-refractory ICANS. CRS/ICANS improvement was observed among 73% of patients; higher response rates in patients receiving higher doses (8 mg/kg per d).33
Anakinra	Prophylactic34	#NCT04148430: 31 patients received anakinra starting on d 2 or after 2 documented fevers of ≥38.5°C before day 2, whichever time point was earlier. The overall severe ICANS rate was 6%. Other ongoing clinical trials include #NCT04432506, #NCT04359784, #NCT04150913, and #NCT04205838.
Tocilizumab	Therapeutic	Approved for use in CRS but is not effective for isolated neurotoxicity and may be associated with worsening neurotoxicity.27
Tocilizumab	Prophylactic35	Not recommended. ZUMA-1 C3, which incorporated prophylactic tocilizumab on d 2 after axi-cel had grade ≥3 NEs 41% compared with 28% in C1+2.35
Siltuximab	Therapeutic	Ongoing clinical trial #NCT04975555. No data available.
Siltuximab	Prophylactic	Ongoing clinical trial #NCT05665725. No data available.
Intrathecal therapy	Therapeutic36,37	2 cases were treated with a rapid and sustained resolution of ICANS.10 Use with other immunosuppressive agents may be associated with sepsis.

We provided the references, when available, for using a specific approach as a therapeutic or prophylactic strategy, otherwise, the use of these agents is anecdotal in nature. Please note that ZUMA-1 cohorts do not represent randomized data.

C, cohort; NEs, neurologic events.