Comparison of CRS- and Icans-Related Outcomes for Large B Cell Lymphoma Patients Treated with Commercial Axicabtagene Ciloleucel with or without Prophylactic Dexamethasone
Authors: Carulli Alison , Elliott Hayden , Mangan Brendan , Whittenburg James , Chong Elise A. , Nasta Sunita D. , Svoboda Jakub , Barta Stefan K. , Porter David L. , Carter Jordan S. , Cook Michael Roderick , Hossain Nasheed , Gill Saar , Garfall Alfred L. , Catania Christopher , Kucharczuk Colleen R. , Schuster Stephen J. , Frey Noelle , Landsburg Daniel J. 
Published: December 2024

Introduction
While large B cell lymphoma (LBCL) patients (pts) treated with axicabtagene ciloleucel (axi-cel) can experience favorable response/survival, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANs) remain significant complications. Use of dexamethasone (dex) prophylaxis (ppx) in cohort 6 of ZUMA-1 resulted in lower rates of CRS/ICANs and similar response rates as compared to the larger study population (PMID 34296427). We aimed to determine the impact of dex ppx on toxicity and efficacy as well as inpatient (ipt) resource utilization outcomes for LBCL pts treated with axi-cel at our institution.
Methods
We performed a retrospective analysis of LBCL pts infused with axi-cel from March 2018-March 2024 at the University of Pennsylvania. All pts received axi-cel in the ipt setting. Dex ppx was given as 10 mg daily on days (d) 0-2 from axi-cel infusion and was prescribed at the discretion of the treating physician. CRS and ICANS were graded using ASTCT consensus criteria.
Results
Sixty-three pts were included in the analysis, of which 22 (35%) received dex ppx (dex group) and 41 (65%) did not (no dex group). For the entire cohort, 13 (21%) pts were age ≥65 years, 21 (33%) female, 28 (44%) received ≥2 prior lines of therapy, 7 (11%) had ECOG performance status ≥2, 44 (70%) received bridging therapy, 20 (32%) had elevated lactate dehydrogenase (LDH) at the time of infusion and 23 (37%) had complete/partial response on imaging prior to infusion. Lymphodepleting chemotherapy (LDC) received was fludarabine/cyclophosphamide (Flu/Cy) in 32 (51%), bendamustine in 30 (48%) and Cy only in 1 (3%) pts. A lower proportion of pts received ≥2 prior LOT (9% vs 63%, P&lt;0.01) and Flu/Cy LDC (18% vs 68%, P&lt;0.01) in the dex vs no dex groups. The remaining baseline characteristics were similar between dex vs no dex groups.
Any grade CRS was detected in 54 (86%) pts, with 17 (77%) in the dex group and 37 (90%) in the no dex groups (P=0.17). Grade ≥3 CRS was detected in 6 (10%) pts, with 1 (5%) in the dex group and 5 (12%) in the no dex group (P=0.34). Median time to onset of CRS was 3 (interquartile range [IQR] 1-4) d, with 3 (IQR 3-5) d in the dex group and 2 (IQR 1-4) d in the no dex group (P=0.02). Median duration of CRS was 4 (IQR 3-7) d with 3 (IQR 2-4) d in the dex group and 5 (IQR 4-7) d in the no dex group (P&lt;0.01). Tocilizumab was given for treatment of CRS to 22 (35%) pts, with 7 (32%) in the dex group and 15 (37%) in the no dex group (P=0.97).
Any grade ICANs was detected in 16 (25%) pts, with 3 (14%) in the dex group and 13 (32%) in the no dex groups (P=0.13). Grade ≥3 ICANs was detected in 9 (14%) pts, with 1 (5%) in the dex group and 8 (20%) in the no dex group (P=0.14). Median time to onset of ICANS was 5 (IQR 4-8) d with 10 (IQR 8-10) d in the dex group and 4 (IQR 4-5) d in the no dex group (P=0.03). Median duration of ICANS was 3 (IQR 2-8) d with 2.5 (IQR 1.5-2.5) d in the dex group and 4 (IQR 3-9) d in the no dex group (P=0.31). Dex was given for treatment of ICANs all pts with ICANs, and the median duration of dex treatment was 7 (IQR 4-10) d with 7 (IQR 5-11.5) d in the dex group and 7 (IQR 4-10) d in the no dex group (P=0.95).
Complete response (CR) 3 months post-infusion was achieved by 27 (43%) pts, with 8 (36%) pts in the dex group and 19 (46%) pts in the no dex group (P=0.31).
The median length of stay (LOS) from the date of axi-cel infusion was 12 (IQR 9-16) d, with 9 (IQR 8-14) d in the dex group and 13 (IQR 10-17) d in the no dex group (P=0.01). ICU transfer for management of CRS and/or ICANs was reported for 7 (11%) pts with 1 (5%) in the dex group and 6 (15%) in the no dex group (P=0.19). Median ICU LOS was 6.5 (IQR 2.5-8) d, with 2 d in dex group and 7 (IQR 3-8) d in no dex group (P=0.27). Seven (11%) pts were readmitted for CRS and/or ICANs management, with 4 (18%) in the dex group and 3 (7%) in the no dex group (P=0.20). The median readmission LOS was 6 (IQR 2-10) d, with 3.5 (IQR 1-7.5) d in the dex group and 7 (IQR 6-12) d in the no dex group (P=0.16).
Conclusion
R/R LBCL pts treated with axi-cel receiving dex ppx experienced significantly longer time to onset of CRS/ICANs but similar incidence, severity and ipt resource utilization for management as compared to those not receiving dex ppx. Our results may inform strategies used to monitor for toxicity in LBCL pts treated with axi-cel with or without dex ppx, recognizing that outpatient infusion/monitoring of axi-cel for LBCL pts receiving dex ppx is currently under investigation through ZUMA-24.