Session: 628. Aggressive Lymphomas: Cellular Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Practice (Health Services and Quality), Lymphomas, Non-Hodgkin lymphoma, Clinical Research, Health outcomes research, Diseases, Real-world evidence, Aggressive lymphoma, Lymphoid Malignancies
Methods: This multicenter international observational study included adult patients treated with autologous CD19 CAR-T cells for large B-cell lymphoma (LBCL). We documented all antibiotic exposures from lymphodepletion initiation to 30 days post-infusion. Exposure between the start of lymphodepletion and the day preceding infusion was defined as pre-CAR-T, while exposure from the day of infusion to 30 days post-infusion was defined as post-CAR-T. Patients exposed to CS or PIM pre-CAR-T were excluded from the post-CAR-T analysis. We constructed multivariable logistic regression and Cox regression models to evaluate response and survival-related outcomes, respectively. All antibiotic exposure models were adjusted for age, pre-lymphodepletion LDH levels, bridging therapy, CAR-T product, and center. Post-CAR-T models were landmarked at day 30 post-infusion and adjusted for the occurrence of CRS.
Results: Among the 956 patients, the median age was 63 (IQR 52-70). Most patients (60%) were treated in US centers, with the remainder in European centers. Bridging therapy was administered to 69% of patients. Axi-cel was the most common CAR-T product (40%), followed by tisa-cel (35%), liso-cel (12%), and a CD19-point-of-care academic product (13%).
In the pre-CAR-T period, 12% of patients were exposed to broad-spectrum antibiotics (PIM and/or CS); 10% to PIM and 2.5% to CS, with 7 patients exposed to both. Post-CAR-T, 75% of patients experienced CRS. Additionally, 67% of patients were exposed to broad-spectrum antibiotics, with significant variation across centers. PIM was used in 56% of patients, with center-specific rates ranging from 10% to 90%. CS were used in 16% of patients, with rates ranging from 0% to 41%. The median duration of post-CAR-T broad-spectrum antibiotic exposure was 9 days (IQR 6-12). Post-CAR-T bloodstream infections were rarely identified, and antibiotic treatment was predominantly empiric.
In multivariable regression models, pre-CAR-T exposure to either PIM and/or CS was associated with a decreased likelihood of complete response (CR) (OR 0.50 [95% CI 0.30-0.82]), shorter overall survival (OS) (HR 2.12 [1.57-2.85]), and progression-free survival (PFS) (HR 1.66 [1.24-2.22]). When considered independently, both PIM and CS maintained a detrimental association with OS.
After multivariable adjustment, post-CAR-T exposure to either PIM and/or CS was not associated with CR, OS, or PFS. However, when PIM was considered independently, it was associated with shorter OS compared to non-exposed patients (HR 1.49 [1.00-2.11]). In multivariable Cox regression models, patients with post-CAR-T exposure to either PIM and/or CS for 10 days or more had shorter OS (HR 1.55 [1.01-2.37]), but not inferior PFS or CR, compared to those with no exposure. Notably, patients with exposure >10 days had higher pre-CAR-T LDH and more severe CRS and ICANS. Shorter exposure (<10 days) was not associated with lower OS or PFS or lower CR rates compared to no exposure.
Conclusions and Perspectives: In this large international multicenter study, two-thirds of patients were exposed to broad-spectrum antibiotics after CAR-T cell infusion, often for durations exceeding a week. Importantly, initiation of broad-spectrum antibiotics after CAR-T infusion with an exposure of less than 10 days did not appear to compromise anti-lymphoma treatment efficacy. These findings may help guide antibiotic use in patients undergoing CAR-T therapy.
Disclosures: Ghilardi: Vittoria Biotherapeutics: Honoraria. Peled: Seres Therapeutics: Patents & Royalties, Research Funding; Crestone Inc: Consultancy; CSL Behring: Consultancy; DaVolterra: Consultancy; Postbiotics Plus Research: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Canaccord Genuity, Inc: Consultancy; MaaT Pharma: Consultancy; Prodigy Biosciences: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Nasta: MERCK: Other: DSMB; Acrotech: Membership on an entity's Board of Directors or advisory committees; ADCT: Membership on an entity's Board of Directors or advisory committees; GenMab: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; Loxo/Lilly: Research Funding; FortySeven/Gilead: Research Funding; ATAEA: Research Funding; ASTEX: Research Funding; ONO therapeutics: Research Funding; Caribou Biosciences: Research Funding. Rejeski: BMS/celgene: Consultancy, Honoraria; Pierre-Fabre: Other: Travel support; novartis: Honoraria; kite/gilead: Consultancy, Honoraria, Other: Travel support, Research Funding. Boardman: Bristol Myers Squibb: Consultancy; OncLive: Honoraria; Cancer Study Group, LLC: Consultancy. Scordo: Miltenyi Biotec: Consultancy; Sanofi: Research Funding; Kite - A Gilead Company: Consultancy; Angiocrine Biosciences, Inc.: Research Funding; MJH Life Sciences (Cancer Network): Honoraria; IDEOlogy: Honoraria; Medscape: Honoraria; Amgen: Research Funding; Omeros Corporation: Consultancy, Research Funding. Falchi: Genentech, Roche, Genmab, AbbVie, Innate, BeiGene: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EvolveImmune: Consultancy; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Taylor Francis: Other: Journal Editor; Genmab: Consultancy, Research Funding; Genentech, Roche, Genmab, Abbvie, Sanofi, EvolveImmune: Honoraria; Kaplan: Other: CME Presentation: Projects in Knowledge; Roche: Consultancy, Research Funding; Memorial Sloan Kettering Cancer Center: Current Employment; AbbVie, Genentech, ADC Therapeutics, Seagen, Ipsen: Membership on an entity's Board of Directors or advisory committees. Svoboda: TG Therapeutics: Honoraria; Adaptive: Honoraria, Research Funding; Merck: Honoraria; Abbvie: Honoraria; Atara: Honoraria; BMS: Honoraria; Incyte: Research Funding; Seagen: Honoraria; GenMab: Honoraria. Chong: Nurix: Research Funding; CARGO: Research Funding; Genentech/Roche: Research Funding; AbbVie: Research Funding; AstraZeneca: Consultancy, Research Funding; Beigene: Consultancy; Genmab: Research Funding. Barta: Kyowa Kirin: Consultancy; BMS: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees; Acrotech: Consultancy; Daiichi Sankyo: Consultancy. Landsburg: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GenMab: Honoraria; Calithera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Shah: Janssen, Amgen, Beyond Spring, BMS, GPCR, DSMB with ArcellX.: Research Funding. Palomba: Bristo Meyer Squibb: Consultancy; Synthekine: Consultancy; Novartis: Consultancy; Cellectar: Consultancy. Salles: BMS/Celgene: Consultancy; Genentech/Roche: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Kite/Gilead: Consultancy; Incyte: Consultancy; Genmab: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Merck: Consultancy; Ipsen: Consultancy, Research Funding; BeiGene: Consultancy; Molecular Partners: Consultancy; Nurix: Research Funding. Park: Takeda: Consultancy; Autolus, Fate Therapeutics, Genentech, InCyte, Servier, Sobi, Takeda (Institution): Research Funding; Curocell: Current equity holder in publicly-traded company; Adaptive Biotechnologies, Affyimmune, Allogene, Amgen, Artiva Biotherapeutics, Autolus, Bright Pharmaceutical Services, BMS, Caribou Biosciences, Curocell, Galapagos, Gilead Sciences, Intellia, In8Bio, Kite, Novartis, Pfizer, Servier, Sobi, Synthekine: Consultancy. Schuster: viTToria biotherapeutics: Consultancy; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Nordic Nanovector: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Legend Biotech: Consultancy, Honoraria; Kite Pharmaceuticals: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Genmab: Consultancy; AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Celgene/Juno Therapeutics: Consultancy, Honoraria, Research Funding; Caribou Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioNTech: Consultancy; BeiGene: Consultancy, Honoraria. Subklewe: Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi Biotec, Molecular Partners, Novartis, Roche, Seagen, Takeda: Research Funding; AbbVie, Amgen, Autolus, AvenCell, BMS, CanCell Therapeutics, Genmab US, Gilead, Ichnos Sciences, Incyte Biosciences, Interius BioTherapeutics, Janssen, Miltenyi Biomedicine, Molecular Partners, Nektar Therapeutics, Novartis, Orbital Therapeutics, Pfizer,: Honoraria; AstraZeneca, BMS, Gilead/Kite, GSK, Janssen, LAWG, Novartis, Pfizer, Roche, Springer Healthcare: Speakers Bureau. Avigdor: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Ascentage: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; TG Therapeutics: Consultancy; Karyospharm: Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Perales: Adicet: Consultancy; Caribou Biosciences: Consultancy; Allogene: Consultancy, Research Funding; VectivBio AG: Consultancy; NexImmune: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Omeros: Current equity holder in publicly-traded company; OrcaBio: Current equity holder in publicly-traded company; ImmPACT Bio: Consultancy; Karyopharm: Consultancy; Merck: Consultancy; OrcaBio: Consultancy; Miltenyi Biotec Incorporated: Consultancy; Kite Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Sanofi S.A.: Consultancy; Nektar Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Jazz Pharmaceuticals: Consultancy; Miltenyi Biotec: Consultancy, Research Funding; Sellas Life Sciences: Research Funding; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy. Ruella: Vittoria Biotherapeutics: Current equity holder in private company, Patents & Royalties; AbClon Inc.: Other: Consultancy, Research Funding.
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