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

Medientyp: E-Artikel
Titel: The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
Beteiligte: Rejeski, Kai; Perez, Ariel; Iacoboni, Gloria; Penack, Olaf; Bücklein, Veit; Jentzsch, Liv; Mougiakakos, Dimitrios; Johnson, Grace; Arciola, Brian; Carpio, Cecilia; Blumenberg, Viktoria; Hoster, Eva; Bullinger, Lars; Locke, Frederick L; von Bergwelt-Baildon, Michael; Mackensen, Andreas; Bethge, Wolfgang; Barba, Pere; Jain, Michael D; Subklewe, Marion
Erschienen: BMJ, 2022
Erschienen in: Journal for ImmunoTherapy of Cancer
Sprache: Englisch
DOI: 10.1136/jitc-2021-004475
ISSN: 2051-1426
Schlagwörter: Cancer Research ; Pharmacology ; Oncology ; Molecular Medicine ; Immunology ; Immunology and Allergy
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Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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<jats:sup>high</jats:sup> 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<jats:sup>high</jats:sup> (16% vs 46%, p<0.001), but not HT<jats:sup>low</jats:sup> patients (0% vs 2%, p=n.s.). Collectively, HT<jats:sup>high</jats:sup> 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<jats:sup>high</jats:sup> patients was observed (8.0% vs 3.7%, p=0.09).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These data demonstrate the utility of the HT score to risk-stratify patients for infectious complications and poor survival outcomes <jats:italic>prior</jats:italic> to CD19 CAR-T. High-risk patients likely benefit from anti-infective prophylaxis and should be closely monitored for potential infections and relapse.</jats:p></jats:sec>
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