Dexamethasone Prophylaxis Reduces Severe Neurotoxicity in CAR-T Therapy Without Compromising Efficacy
核心洞察
Dexamethasone prophylaxis significantly reduced grade 3/4 immune effector cell-associated neurotoxicity syndrome (搜索) (ICANS) from 25% to 0% in patients receiving axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma (搜索).
The steroid treatment did not compromise CAR-T cell efficacy, with comparable overall response rates (89% vs 75%) and survival outcomes between prophylaxis and control groups.
Peak absolute lymphocyte counts were significantly higher in dexamethasone-treated patients (750 vs 500 cells/μL), suggesting enhanced immune cell expansion rather than suppression.
A single-institution retrospective study presented at the 2025 American Society of Hematology Annual Meeting demonstrates that dexamethasone prophylaxis significantly reduces severe neurotoxicity associated with axicabtagene ciloleucel (Yescarta) CAR-T therapy in patients with relapsed or refractory large B-cell lymphoma (搜索), without compromising treatment efficacy.
The study, conducted at Fox Chase Cancer Center, analyzed 44 patients treated with axicabtagene ciloleucel, with 28 receiving dexamethasone prophylaxis and 16 serving as controls. Patients in the prophylaxis group received 10 mg oral dexamethasone on days 0, 1, and 2 after CAR-T cell infusion.
Significant Reduction in Severe Neurotoxicity
The most striking finding was the complete elimination of grade 3 or 4 immune effector cell-associated neurotoxicity syndrome (搜索) (ICANS) in the dexamethasone group, compared to 25% occurrence in the control group (P = .013). Dr. Christina Darwish, a second-year fellow who presented the data, noted that "the rates of grade 3 or 4 ICANS were significantly lower among those who did receive dexamethasone prophylaxis."
While the overall ICANS rate was numerically lower in the dexamethasone group (21% vs 38%), this difference did not reach statistical significance (P = .30). Grade 1 ICANS occurred in 21% of prophylaxis patients versus 13% of controls, with no grade 2 events observed in either group.
Cytokine Release Syndrome Rates Unchanged
Dexamethasone prophylaxis did not significantly alter cytokine release syndrome (搜索) (CRS) patterns. Total CRS rates were nearly identical between groups (71% vs 69%, P = 1.00). Grade 1, 2, and 3 CRS occurred in 46%, 25%, and 0% of dexamethasone patients compared to 38%, 31%, and 0% in controls, respectively.
Preserved Treatment Efficacy
Contrary to historical concerns about steroids potentially limiting CAR-T cell expansion, the study revealed comparable or potentially improved efficacy outcomes. Overall response rates were 89% in the dexamethasone group versus 75% in controls (P = .21), while complete response rates were 79% and 69%, respectively (P = .47).
Long-term survival outcomes remained similar between groups, with two-year overall survival of 72.2% versus 67.7% (P = .67) and progression-free survival of 49.9% versus 60.6% (P = .28) for dexamethasone and control groups, respectively.
Enhanced Immune Cell Expansion
Peak median absolute lymphocyte count was significantly higher in the prophylaxis group at 750 cells/μL compared to 500 cells/μL in controls (P = .01). Additionally, the median time to peak absolute lymphocyte count was shorter in dexamethasone-treated patients at 9.5 days versus 17 days (P = .08), suggesting enhanced rather than suppressed immune cell expansion.
Patient Demographics and Treatment Details
The study population had a median age of 63 years in the dexamethasone group and 62 years in controls. Most patients in the prophylaxis group had diffuse large B-cell lymphoma (搜索) (68%), followed by follicular lymphoma (搜索) (29%) and primary mediastinal B-cell lymphoma (搜索) (4%). The control group had similar distribution with 63% diffuse large B-cell lymphoma, 19% follicular lymphoma, 13% high-grade B-cell lymphoma (搜索), and 6% marginal zone lymphoma (搜索).
Advanced disease was common, with 92% versus 73% having Lugano stage III-IV disease in the dexamethasone and control groups, respectively. Most patients (96%) in the prophylaxis group received bendamustine for lymphodepletion, while controls primarily received fludarabine and cyclophosphamide.
Clinical Context and Future Implications
These findings address longstanding concerns about steroid use in CAR-T therapy. As Darwish explained, "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, the results align with previous safety cohort data from the ZUMA-1 trial, which showed that dexamethasone prophylaxis enhanced safety without compromising efficacy.
The median follow-up was 21.4 months for the dexamethasone group and 32.5 months for controls, providing substantial long-term outcome data. The study utilized Fisher's exact test for categorical variables, Kaplan-Meier method for survival analysis, and Mann-Whitney test for continuous variables to ensure statistical rigor.