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Baseline serum inflammatory proteins predict poor CAR T outcomes in diffuse large B-cell lymphoma.

Rawan G FaramandSae Bom LeeMichael D JainBiwei CaoXuefeng WangMarion SubkleweMarion SubkleweJohannes F FahrmannNeeraj Y SainiSamir M HanashYun Pyo KangDarwin ChangPaulo C RodriguezErin A DeanTaiga NishihoriBijal D ShahAleksander LazaryanJulio C ChavezFarhad KhimaniJavier A Pinilla-IbarzMarian DamKayla M ReidSalvatore A CoralloMeghan MengesMelanie Hidalgo VargasJessica K MandulaBrian A HollidayChristina A BachmeierKelly A SpethQinghua SongMike MattieFrederick L LockeMarco L Davila
Published in: Blood cancer discovery (2024)
A subset of patients with diffuse large B cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor T cell (CAR T) therapy have poor clinical outcomes. We report serum proteins associated with severe immune mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel. We develop a simple stratification based on pre-lymphodepletion CRP and ferritin to classify patients into low, intermediate and high-risk groups. We observe that patients in the high-risk category were more likely to develop grade ≥3 toxicities and had inferior overall and progression-free survival. We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T cell therapy.
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