High-Grade ICANS Severity Decreases Via Dexamethasone After Axi-Cel in LBCL

"Our study shows that, overall, there were no significant differences in rates of CRS and ICANS in general with dexamethasone prophylaxis," according to study investigator Christina Darwish, MD.

Retrospective data presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition showed that prophylactic dexamethasone following treatment with axicabtagene ciloleucel (axi-cel; Yescarta) for relapsed/refractory large B-cell lymphoma (LBCL) did not influence the incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) or cytokine release syndrome (CRS), although the severity of grade 3/4 ICANS was reduced.1

Furthermore, peak absolute lymphocyte counts (ALC) was higher in patients who received dexamethasone prophylaxis, and survival outcomes were comparable between groups.

“Our study shows that, overall, there were no significant differences in rates of CRS and ICANS in general with dexamethasone prophylaxis,” said Christina Darwish, MD, a second-year fellow at Fox Chase Cancer Center at Temple University Hospital in Philadelphia, Pennsylvania, who presented the data. “However, the rates of grade 3 or 4 ICANS were significantly lower among those who did receive dexamethasone prophylaxis.”

Dexamethasone’s Effect on CRS and ICANS

Of statistical significance, no grade 3 or 4 ICANS events occurred in the dexamethasone group vs 25% in the no-dexamethasone group (P = .013). The total rate of ICANS events was lower in the group that received dexamethasone (21%) compared with the group that did not, but this difference did not reach statistical significance (38%; P = .30).

No grade 2 ICANS events occurred in either group, and 21% vs 13% in the dexamethasone and no-dexamethasone groups, respectively, had grade 1 ICANS.

Rates of grade 1, grade 2, and grade 3 CRS were 46%, 25%, and 0% in the dexamethasone group compared with 38%, 31%, and 0% in the no-dexamethasone group, respectively. Total CRS rates were 71% and 69% in the groups, respectively (P = 1.00).

Did Dexamethasone Affect Axi-Cel Efficacy?

Prolonged follow-up demonstrated an overall response rate (ORR) of 89% vs 75% in the dexamethasone and no-dexamethasone groups, respectively (P = .21). Compete response rates (CR) were 79% and 69%, respectively (P = .47). Two-year overall survival (OS) was 72.2% vs 67.7% (P = .67), and progression-free survival (PFS) was 49.9% vs 60.6% (P = .28), respectively.

Peak median ALC was 750 cells/µL vs 500 cells/µL in prophylaxis and no-prophylaxis groups, respectively (P = .01). Median time to peak ALC was shorter in the dexamethasone group at 9.5 days vs 17 days in the no-dexamethasone group (P = .08).

Median follow-up for the analysis was 21.4 months in the dexamethasone group and 32.5 months in the no-dexamethasone group.

Study Design and Patient Characteristics

Forty-four patients were treated with axi-cel, and 28 received dexamethasone prophylaxis, while 16 did not. Those who received dexamethasone prophylaxis received the steroid at 10 mg orally on days 0, 1, and 2 after axi-cel infusion.

Most patients in the dexamethasone group had diffuse large B-cell lymphoma (DLBCL; 68%), followed by follicular lymphoma (29%), and primary mediastinal B-cell lymphoma (PMBCL, 4%). No patients in the dexamethasone group had high-grade B-cell lymphoma (HGBCL) or marginal zone lymphoma (MZL).

In the no-dexamethasone group, 63% had DLBCL, 19% had follicular lymphoma, 13% had HGBCL, and 6% had MZL. No patients in this group had PMBCL.

Patients in the dexamethasone and no-dexamethasone groups had a median age of 63 years (range, 42-80) and 62 years (range, 43-74), respectively; 92% vs 73% had Lugano stage III to IV disease; 71% vs 75% had high-grade lymphoma; 18% vs 13% had bulky disease; and 75% of each group received bridging therapy. With regard to lymphodepleting therapy, most patients in the dexamethasone group received bendamustine (96%), and most patients in the no-dexamethasone group received fludarabine and cyclophosphamide.

Most patients in the dexamethasone group (93%) and no dexamethasone group (94%) had an ECOG performance status of 0 to 1; 4% vs 6%, respectively, had a score of 2; and 4% vs 0% had a score of 3. Fifty-seven percent of the dexamethasone group was male vs 31% in the no-dexamethasone group.

Fisher’s exact test was used to compare categorical variables, and the Kaplan-Meier method was used for survival analysis. The Mann-Whitney test was used to compare continuous variables.

Background on the Study

Axi-cel, a CD19-targeting CAR T-cell therapy, is approved for the treatment of patients with LBCL relapsed or refractory to chemoimmunotherapy within 12 months of frontline treatment, as well as for the treatment of patients with relapsed or refractory LBCL following 2 or more lines of systemic therapy including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL occurring as a result of follicular lymphoma.2

The agent also received accelerated approved for the treatment of patients with relapsed or refractory follicular lymphoma following 2 or more lines of prior systemic therapy.

According to Darwish, previous concerns have existed regarding the use of steroids in CAR T-cell therapies due to worry that steroids may limit CAR T-cell expansion and efficacy following infusion. However, results from a safety cohort of the phase 1/2 ZUMA-1 trial (NCT02348216) revealed that dexamethasone prophylaxis enhanced safety of axi-cel without compromising efficacy.3

References

1. Darwish C, Khanal R, Gandler H, et al. Long-term outcomes of dexamethasone prophylaxis after axicabtagene ciloleucel for non-Hodgkin lymphoma: a single-center retrospective study. Blood. 2025;146(Supplement 1):4539. doi:10.1182/blood-2025-4539
2. Yescarta. Prescribing information. Gilead Sciences; 2025. Accessed December 9, 2025. https://www.gilead.com/-/media/files/pdfs/medicines/oncology/yescarta/yescarta-pi.pdf
3. Oluwole OO, Forcade E, Muñozz J, et al. Prophylactic corticosteroid use with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL): 2-year follow-up of ZUMA-1 cohort 6. Blood. 2022;140(Supplement 1). doi:10.1182/blood-2022-156117