Introduction: In Cohorts 1+2 of the ZUMA-1 Phase 1/2 study of axi-cel in R/R LBCL, 11% and 31% of patients (pts) experienced Grade ≥3 cytokine release syndrome (CRS) or neurologic evenets), respectively. To minimize the toxicities seen with axi-cel, a safety management cohort, Cohort 6 (N=40), was added to evaluate whether prophylactic (ppx) corticosteroids (CS) could decrease grade ≥ 3 CRS or ICANS. The 2-year update of ZUMA-1 Cohort 6 showed no grade ≥3 CRS and 15% grade ≥3 ICANS without any difference in objective response rate (ORR) or complete response rate (CR) when compared to cohorts 1+2 (Oluwole Blood 2022). The FDA had previously approved an update to the prescribing information for axi-cel to include use of ppx CS across all approved indications in January 2022. However, ppx CS is not a mandatory standard treatment and we sought to establish the clinical outcomes in the real-world practice.

Methods: To assess the clinical outcomes of pts receiving ppx CS, we conducted a multicenter retrospective analysis of pts with R/R LBCL who were treated with axi-cel since the FDA approval of ppx CS in January 2022. Baseline characteristics, toxicities, and efficacy were compared between the no ppx and ppx CS groups. CRS and ICANS were graded based on ASTCT 2019 guidelines. Event-free survival (EFS) was defined as time from axi-cel infusion to progression, re-treatment, or death. Overall survival (OS) was defined as time from axi-cel infusion to death due to any cause.

Results: A total of 66 pts at 5 centers received axi-cel between Jan 31, 2022, and June 20, 2023. Thirty-five (52%) pts received ppx CS, with a median age of 63 years (26-85 years). By histology, 75% (n=50) of the pts had DLBCL, 13.6% (n=9) had high grade B-cell lymphoma (HGBL), 9.1% (n=6) had transformed follicular lymphoma (TFL) and 1.5% (n=1) primary mediastinal LBCL (PMBCL). 59% of the pts (n=37) had IPI >2 and 66% (n=43) had stage III/IV disease. The baseline characteristics at the time of apheresis are shown in Table 1 and were comparable between the 2 groups, except for more HGBL, fewer prior lines of therapy and longer median time from apheresis to axi-cel infusion in the ppx CS group. Among the entire cohort, only 37% (n=25) met ZUMA-1 eligibility criteria at the time of lymphodepletion, and 67% (n=44) needed bridging therapy. Any grade CRS occurred in 88% (n=58) of the pts, with grade ≥2 CRS in 38% (n=25). Any grade ICANS occurred in 55% (n=37) of the pts, with grade ≥2 ICANS in 41% (n=27). Any grade ICANS was significantly lower in the ppx CS group than the no ppx group (45.7% vs 65.5%). The rates of any grade CRS, grade ≥2 CRS, grade ≥2 ICANS, the median time to CRS onset, ICANS onset, CRS duration, and ICANS duration were comparable between the 2 groups. Tocilizumab and steroids use was similar between two groups with a trend towards less ICU admission in patients in the ppx CS group. Overall, 14 (21%) pts developed infectious complications within 30 days of axi-cel infusion. The day 30 ORR was 84% and was comparable between the 2 groups (77% in the ppx group vs 93% in the no ppx group). The CR was 45.7% in ppx CS group compared to 65.5% in no ppx group. At a median follow up of 219 days (27-1178), 37 (56.1%) pts had progressed and 25 (37.9%) pts had died. The number of days to progress was significantly lower in the ppx CS arm. The median EFS and OS were not significant between the 2 groups.

Conclusions: This multicenter retrospective study showed that the efficacy of treatment with axi-cel in R/R LBCL did not decrease with the use of ppx CS. No significant differences in efficacy or CAR-T-associated toxicities were noted in the 2 groups, potentially due to selective use with patients at presumed higher risk of severe CRS and ICANS. A larger dataset and longer follow-up is needed for risk-stratified analysis and the study is ongoing.

Munoz:ADC Therapeutics: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Epizyme: Consultancy; Morphosys/Incyte: Consultancy; TG Therapeutics: Consultancy; Acrotech/Aurobindo: Consultancy, Speakers Bureau; Beigene: Consultancy, Research Funding, Speakers Bureau; Physicians' Education Resource: Honoraria; Curio: Honoraria; Verastem: Consultancy, Speakers Bureau; Celgene: Research Funding; Celgene/ Bristol-Myers Squibb: Consultancy, Speakers Bureau; Lilly/Loxo: Consultancy; MEI: Consultancy; Kyowa: Honoraria, Speakers Bureau; Alexion: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Karyopharm: Consultancy; Genmab: Consultancy; Merck: Research Funding; Portola: Research Funding; Incyte: Research Funding; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; Millennium: Research Funding; Targeted Oncology: Honoraria; OncView: Honoraria; Pharmacyclics/ Janssen: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics/Abbvie: Consultancy, Research Funding. Hunter:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Genmab: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Notable Labs: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Speakers Bureau; Genentech: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Patel:Curis, Inc: Research Funding; CRISPR Therapeutics: Research Funding; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Epizyme: Consultancy, Research Funding; Fate Therapeutics: Research Funding; Genentech/Roche: Consultancy, Research Funding; Kite: Consultancy, Research Funding, Speakers Bureau; Loxo Oncology: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Morphosys: Consultancy; Nurix: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; Sunesis Pharmaceuticals: Research Funding; TG Therapeutics: Consultancy, Speakers Bureau; Trillium Therapeutics/Pfizer: Consultancy, Research Funding; Xencor: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Research Funding; Abbvie: Consultancy. Wang:Eli Lilly: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Innocare: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genmab: Research Funding; Genentech: Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy. Paludo:Karyopharm: Research Funding; Biofourmis: Research Funding; AbbVie: Consultancy. Bennani:Secura Bio: Other: Advisory board; No personal compensation; Kymera: Other: Advisory board; No personal compensation; Affimed: Other: Advisory board; No personal compensation; Astellas Pharma: Other: Advisory board; No personal compensation; Acrotech: Other: Advisory board; No personal compensation; Acrotech: Other: Scientific Advisory Committee, No personal compensation . Ansell:Bristol-Myers Squibb: Other: Contracted Research; Pfizer, Inc: Other: Contracted Research; Regeneron Pharmaceuticals Inc: Other: Contracted Research; Seagen Inc: Other: Contracted Research; Affirmed: Other: Contracted Research; ADC Therapeutics: Other: Contracted Research; Takeda Pharmaceuticals USA Inc: Other: Contracted Research.

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