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4889 Patterns and Safety of Glucocorticosteroids Use Following CD19 CAR-T Cell Therapy for B-Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 705. Cellular Immunotherapies: Late Phase and Commercially Available Therapies: Poster III
Hematology Disease Topics & Pathways:
adult, Biological therapies, Research, Lymphomas, non-Hodgkin lymphoma, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Clinical Research, Diseases, indolent lymphoma, Therapies, Immunotherapy, real-world evidence, aggressive lymphoma, Lymphoid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Efrat Luttwak, MD1, Jessica R. Flynn, MS2*, Sean M. Devlin, PhD3*, Giulio Cassanello4*, Magdalena Corona, MD4*, Parastoo B. Dahi, MD4,5*, Alejandro Luna De Abia, MD, PhD4*, Joshua Fein, MD6*, Sergio A. Giralt, MD, FACP4, Ivan Landego, MD4*, Richard J. Lin, MD, PhD4, Maria Lia Palomba, MD7,8, Allison Parascondola, MPH4*, Jae H. Park, MD4, Amethyst Saldia, BS4*, Michael Scordo4, Ana Alarcon Tomas, MD4*, Gunjan L. Shah4,8, Miguel-Angel Perales, MD4,8, Gilles Salles, MD, PhD7,8 and Roni Shouval, MD, PhD4,8*

1Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
2Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York
3Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY
4Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
5Department of Medicine, Weill Cornell Medical College, New York, NY
6Department of Hematology & Medical Oncology, NewYork-Presbyterian/Weill Cornell Medical Center, New York, NY
7Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York
8Department of Medicine, Weill Cornell Medical College, New York

Introduction: CAR T-cell therapy is a well-established therapy for relapsed and/or refractory B cell non-Hodgkin’s lymphomas (R/R B-NHL). However, CAR-T cell therapy may cause significant toxicities such as CRS and ICANS. Glucocorticosteroids play a pivotal role in managing these toxicities but can also suppress T cell function and may impede the persistence and effectiveness of CAR-T cells. The impact of glucocorticosteroids has resulted in conflicting conclusions in the literature.

Objective: This single-center, retrospective, observational study aimed to compare the outcomes of patients with R/R B-NHL who received steroids to those who did not after CAR-T cell therapy.

Methods: Patients’ records were reviewed to identify any steroid administration within 30 days of CAR-T cell infusion. Patients receiving steroids within 7 days before CAR-T infusion were excluded to focus on CAR-T impact without confounding baseline steroid use. Information on the type of steroids, indication, timing and duration was collected. Steroids were expressed as dexamethasone equivalent. Steroids-associated variables were analyzed as both continuous and categorical variables, using median as the threshold. Cox regression models and Kaplan-Meier analysis was employed for PFS and OS estimation using steroids as a time-dependent covariate and a 30-day landmark analysis, with events as disease progression or death for PFS and death only for OS.

Results: 292 patients with R/R B-NHL received commercial CAR-T cell therapy (48% axi-cel, 24% tisa-cel, 22% liso-cel, and 6% Brexu-cel), primarily for large B cell cell lymphoma (85%), mantle cell (11%) or follicular (4%) lymphoma. Only 49 of the 292 patients (17%) received steroids between the day of infusion (day 0) to 30 days after. The median cumulative dexamethasone-equivalent dose at 30 days was 60 mg (range: 1-1982), the median day from CAR-T cells infusion to steroids initiation was 7 days (range 0-26) and the median duration of corticosteroid use was 3 days (range, 1-27). Patients receiving steroids had a significantly higher number of lines of prior therapies (p=0.036), more stage 3-4 disease (p=0.027), and elevated pre-lymphodepletion LDH levels(p=0.004). However, there were no other significant differences, including CD19 CAR-T product type, between the groups.

The rates of grade 2 or higher CRS and ICANS were documented in 42% and 18%, respectively. ICANS (47%), CRS (14%), or both (21%) were the leading indications for steroid administration. Other indications for administration of steroids were progression of disease (n=4), adrenal insufficency (n=3), graft vs host disease (n=1), and premedication with intravenous immune globulin (n=1).

With a median follow-up of 20 months, median PFS and OS were 6.8 months (95% CI 6-11) and 27 months (95% CI 18-not reached), respectively. The use, duration, and cumulative dose of steroids, whether analyzed as continuous or categorial variables in univariable Cox regression models, were not associated with PFS and OS in a 30 landmark analysis (Figure). The analysis of the adminstration of steroids as a time-dependent covariate did not show significant differences for either PFS or OS. Importantly, patients exposed to steroids were also not at increased risk for bloodstream infections (p=0.68).

Conclusion: In this largest analysis to date on the impact of steroids on CAR-T outcomes, steroid exposure following CAR-T cell infusion was not associated with a greater likelihood of CAR-T cell therapy failure. Our results deviate from previous observations that associate using steroids with shorter PFS and OS (Starti et al, Blood 2021, Terao et al, JTCT 2023). The discrepancy is likely due to our study's exclusion of steroid use prior to CAR-T and statistical analysis. Overall, our findings suggest that steroid administration for CAR-T cell therapy toxicity management is safe and does not appear to have a negative impact on efficacy.

Disclosures: Giralt: Amgen, Actinuum, Celgene/BMS, Omeros, Johnson & Johnson, Miltenyi, Takeda: Research Funding; Amgen, Actinuum, Celgene/BMS, Kite Pharma, Janssen, Jazz Pharmaceuticals, Johnson & Johnson, Novartis, Spectrum Pharma, Takeda: Membership on an entity's Board of Directors or advisory committees. Palomba: Seres Therapeutics: Honoraria, Patents & Royalties; Rheos: Honoraria; Synthekine: Honoraria; GarudaTherapeutics: Honoraria; MustangBio: Honoraria; Smart Immune: Honoraria; Thymofox: Honoraria; Novartis: Honoraria; Cellectar: Honoraria; Ceramedix: Honoraria; Juno: Honoraria, Patents & Royalties; Kite: Honoraria; Pluto Immunotherapeutics: Honoraria; BMS: Honoraria. Park: Minerva Bio: Consultancy; Be Biopharma: Consultancy; Affyimmune: Consultancy; BeiGene: Consultancy; Curocell: Consultancy; Kite: Consultancy; Bright Pharmacetuicals: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Genentech, Inc.: Research Funding; Artiva Biotherapeutics: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; GC Cell: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Autolus Therapeutics: Research Funding; Fate Therapeutics: Research Funding; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Research Funding; Intella: Consultancy; Takeda: Consultancy, Research Funding; Sobi: Consultancy, Research Funding. Scordo: Omeros Corporation: Consultancy, Research Funding; Medscape, LLC: Honoraria; CancertNetwork (Intellisphere LLC): Honoraria; Amgen, Inc.: Research Funding; Angiocrine Bioscience, Inc.: Research Funding. Shah: ArcellX: Other: DSMB; BMS: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Beyond Spring: Research Funding. Perales: Takeda: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; DSMB: Other; VectivBio AG: Consultancy, Honoraria; Vor Biopharma: Consultancy, Honoraria; Adicet: Honoraria; Celgene: Honoraria; Cidara Therapeutics: Consultancy, Other; BMS: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Astellas: Consultancy, Honoraria; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Caribou: Consultancy, Honoraria; Equillium: Consultancy, Honoraria; Exevir: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Kite: Consultancy, Honoraria, Research Funding; Servier: Other; Allogene: Research Funding; Allovir: Consultancy; AbbVie: Consultancy, Honoraria; Orcabio: Consultancy, Current equity holder in publicly-traded company, Honoraria; Omeros: Consultancy, Current equity holder in publicly-traded company, Honoraria; Medigene: Consultancy, Other; NexImmune: Consultancy, Current equity holder in publicly-traded company; Syncopation: Honoraria; Nektar Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Sellas Life Sciences: Consultancy. Salles: BeiGene: Consultancy; Molecular Partners: Consultancy; Genmab: Consultancy; Merck: Consultancy, Honoraria; Orna: Consultancy; Nurix: Consultancy; ATB Therapeutics: Consultancy; Incyte: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Debiopharm: Consultancy; Janssen: Consultancy, Research Funding; BMS/Celgene: Consultancy; Kite/Gilead: Consultancy; Nordic Nanovector: Consultancy; AbbVie: Consultancy, Honoraria; EPIZYME: Consultancy; Loxo/Lilly: Consultancy; Owkin: Current holder of stock options in a privately-held company; Ipsen: Consultancy, Research Funding; Novartis: Consultancy.

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