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The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL

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Item Type:Article
Title:The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
Creators Name:Rejeski, K. and Perez, A. and Iacoboni, G. and Penack, O. and Bücklein, V. and Jentzsch, L. and Mougiakakos, D. and Johnson, G. and Arciola, B. and Carpio, C. and Blumenberg, V. and Hoster, E. and Bullinger, L. and Locke, F.L. and von Bergwelt-Baildon, M. and Mackensen, A. and Bethge, W. and Barba, P. and Jain, M.D. and Subklewe, M.
Abstract:BACKGROUND: CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) represents a promising treatment modality for an increasing number of B-cell malignancies. However, prolonged cytopenias and infections substantially contribute to the toxicity burden of CAR-T. The recently developed CAR-HEMATOTOX (HT) score-composed of five pre-lymphodepletion variables (eg, absolute neutrophil count, platelet count, hemoglobin, C-reactive protein, ferritin)-enables risk stratification of hematological toxicity. METHODS: In this multicenter retrospective analysis, we characterized early infection events (days 0-90) and clinical outcomes in 248 patients receiving standard-of-care CD19 CAR-T for relapsed/refractory large B-cell lymphoma. This included a derivation cohort (cohort A, 179 patients) and a second independent validation cohort (cohort B, 69 patients). Cumulative incidence curves were calculated for all-grade, grade ≥3, and specific infection subtypes. Clinical outcomes were studied via Kaplan-Meier estimates. RESULTS: In a multivariate analysis adjusted for other baseline features, the HT score identified patients at high risk for severe infections (adjusted HR 6.4, 95% CI 3.1 to 13.1). HT(high) patients more frequently developed severe infections (40% vs 8%, p<0.0001)-particularly severe bacterial infections (27% vs 0.9%, p<0.0001). Additionally, multivariate analysis of post-CAR-T factors revealed that infection risk was increased by prolonged neutropenia (≥14 days) and corticosteroid use (≥9 days), and decreased with fluoroquinolone prophylaxis. Antibacterial prophylaxis significantly reduced the likelihood of severe bacterial infections in HT(high) (16% vs 46%, p<0.001), but not HT(low) patients (0% vs 2%, p=n.s.). Collectively, HT(high) patients experienced worse median progression-free (3.4 vs 12.6 months) and overall survival (9.1 months vs not-reached), and were hospitalized longer (median 20 vs 16 days). Severe infections represented the most common cause of non-relapse mortality after CAR-T and were associated with poor survival outcomes. A trend toward increased non-relapse mortality in HT(high) patients was observed (8.0% vs 3.7%, p=0.09). CONCLUSIONS: These data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes prior to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse.
Keywords:Adoptive Immunotherapy, CD19 Antigens, Chimeric Antigen Receptors, Diffuse Large B-Cell Lymphoma, Disease Progression, Local Neoplasm Recurrence, Retrospective Studies
Source:Journal for ImmunoTherapy of Cancer
Publisher:BMJ Publishing Group
Page Range:e004475
Date:17 May 2022
Official Publication:https://doi.org/10.1136/jitc-2021-004475
PubMed:View item in PubMed

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