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2274 Real World Outcomes with Evolving Management of Cytokine Release Syndrome in CAR-T Therapy

Program: Oral and Poster Abstracts
Session: 902. Health Services and Quality Improvement: Lymphoid Malignancies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Non-Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Real-world evidence, Lymphoid Malignancies
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Radhika Bansal, MBBS1*, Andre Corraes, MD2*, Monica Shaw3*, Lucy Holmes, ANP4*, Allison Kosobud, PA-C4*, Kelsey L Haugen5*, Arushi Khurana, MBBS2, Paul J. Hampel, MD2, Urshila Durani, MD, MPH2, Suzanne R Hayman, MD2, Yucai Wang, MD, PhD2, Moritz Binder, MD2, Jonas Paludo, MD2, Saad S. Kenderian, MD2, N. Nora Bennani, MD2, Patrick B. Johnston, MD, PhD5*, Stephen M. Ansell, MD, PhD2 and Yi Lin, MD, PhD2

1Internal Medicine, Zucker School of Medicine at Hofstra/Northwell at Lenox Hill, New York, NY
2Division of Hematology, Mayo Clinic, Rochester, MN
3Deptt of hematology, Mayo CliniC, Rochester, MN
4Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, MN
5Mayo Clinic, Rochester, MN

Background:

Management of cytokine release syndrome (CRS) with chimeric antigen receptor T cell therapy (CAR-T) has evolved in the last decade. First line treatment tocilizumab (toci) was initially given for grade 2 or higher CRS in clinical trials (Toci/CRS≥2). Earlier use of toci in grade 1 CRS was found to be safe without negative impact on clinical response in cohort 4 of ZUMA-1 study for axicabtagene ciloleucel (axi-cel) for B-cell non-Hodgkin lymphoma (NHL; Toci/CRS1). This practice was also adopted for other CAR-T therapies for other disease indications. Subsequently, FDA also updated the package insert for axi-cel in 2021 to include the use of prophylactic dexamethasone (ppx dex) to be given on days 0, 1, 2 of CAR-T infusion based on the results from cohort 6 of ZUMA-1. We examined CRS and ICANS (immune effector cell associated neurologic syndrome) outcome of patients who received FDA approved axi-cel in standard-of-care (SOC) practice with these evolving practices. Of note, adoption of ppx dex has been variable across CAR-T treatment centers in the US (Khurana et al, Blood 2022). At Mayo Clinic Rochester, patients considered high-risk for severe CRS/ICANS (those who received bridging therapy and had LDH above upper limit of normal and/or with secondary CNS involvement or other CNS pathologies) would be considered for ppx dex.

Methods:

Medical records of patients who received axi-cel in SOC between 2018 and 2023 at Mayo Clinic Rochester were reviewed. ASTCT guideline was used for CRS and ICANS grading. Categorical variables were compared using Chi-squared test and continuous variables were compared using Kruskal-Wallis test.

Results:

Among 187 pts receiving SOC axi-cel, the median age was 60 years and 121 (65%) were males, 152 (81%) had CRS, of which 73 (39%) were grade ≥2; 97 (52%) had ICANS, of which 65 (35%) were grade ≥2. Of the 152 CRS pts, 54/152 (36%) pts never received toci or ppx/dex. Of the pts who received Toci, 35/152 (23%) received Toci when CRS is at least grade 2 (Toci/CRS≥2), 49/152 (32%) received Toci/CRS1 without ppx dex (Toci/CRS1), and 14 (9%) received ppx dex with Toci given in CRS1 when pts developed CRS (PPX DEX). Baseline demographics were comparable except age (Toci/CRS≥2: 58y; Toci/ CRS1: 63y; ppx dex: 50y; p=0.001) and pre-LD CRP (Toci/CRS≥2: 34mg/L; Toci/ CRS1: 6mg/L; ppx dex: 16mg/L; p=0.002). Pre-LD LDH and ferritin were also comparable.

PPX DEX or Toci/CRS1 had significantly lower rate of maximum grade CRS≥2 (PPX DEX: 4 (29%); Toci/ CRS1: 20 (41%); 35 (100%); p<0.001) and duration of CRS (PPX DEX: 2.5d; Toci/ CRS1: 3d; Toci/CRS≥2: 5d; p<0.001). Time to onset of CRS was not statistically different between the 3 groups. Not surprisingly, Toci/CRS1 group had higher overall rate of toci use, compared to . Interestingly, use rate of ≥2 doses of Toci or siltuximab was significantly higher in Toci/CRS1 or PPX DEX (PPX DEX: 8 (57%); Toci/ CRS1: 26 (53%); 9 (26%); p=0.02).

Pt who received PPX DEX or Toci/CRS1 had a significantly lower rate of ICANS (PPX DEX: 6 (43%); Toci/ CRS1: 33 (67%); 32 (91%); p=0.001) and rate of max grade ICANS ≥2 (PPX DEX: 3 (21%); Toci/ CRS1: 23 (47%); 27 (77%); p<0.001). The time to onset and duration of ICANS was not different among the 3 groups.

Conclusion: Our real-world study shows that earlier use of Toci in grade 1, compared to its first use in grade 2, can result in lower overall incidence of more severe CRS, duration of CRS, incidence of ICANS and more severe ICANS. While we selected patients at higher risk for having more severe CRS in our PPX DEX cohort, experience to date suggests that these patients, compared to toci/CRS>=2 cohort, could also have reduced severity of CRS and ICANS with this updated management.

Disclosures: Bansal: Kite Pharma: Other: Travel Support. Wang: Kite: Honoraria; InnoCare, AbbVie: Consultancy; Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding. Paludo: Biofourmis: Research Funding; Karyopharm: Research Funding; AstraZeneca: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees. Kenderian: Novartis, Humanigen, MustangBio,: Patents & Royalties; Novartis, Kite/Gilead, Juno/BMS, Lentigen, Humanigen, Morphosys, Tolero, LeahLabs, InCyte, Viracta: Research Funding; Novartis, Kite/Gilead, Juno/BMS, Capstan, Humanigen, Carisma: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Novartis, Carisma, Juno/BMS, Humanigen, Luminary: Consultancy. Bennani: Pfizer: Membership on an entity's Board of Directors or advisory committees; Acrotech Biopharma LLC: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board. Johnston: Miltenyi: Consultancy, Other: Honoaria paid to Mayo Clinic. Ansell: Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees, Research Funding; SeaGen: Research Funding; AstraZeneca: Research Funding; Takeda: Research Funding; ADC Therapeutics: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding. Lin: Janssen: Consultancy, Research Funding; Caribou: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; NexImmune: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy; Legend: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy.

*signifies non-member of ASH