The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
Rejeski, Kai (Ludwig-Maximilians-University Hospital)
Perez, Ariel (Miami Cancer Institute, Miami, Florida, USA)
Iacoboni, Gloria (Vall d'Hebron Institut d'Oncologia)
Penack, Olaf (German Cancer Research Center (DKFZ))
Bücklein, Veit (Ludwig-Maximilians-University Hospital)
Jentzsch, Liv (University Hospital of Tübingen (Alemanya))
Mougiakakos, Dimitrios (University of Erlangen-Nuremberg, Germany)
Johnson, Grace (USF Morsani College of Medicine, Tampa, Florida, USA)
Arciola, Brian (USF Morsani College of Medicine, Tampa, Florida, USA)
Carpio Segura, Cecilia del Carmen (Vall d'Hebron Institut d'Oncologia)
Blumenberg, Viktoria (Ludwig-Maximilians-University Hospital)
Hoster, Eva (Institute for Medical Information Processing, Biometry and Epidemiology (IBE), LMU Munich, Germany)
Bullinger, Lars (Freie Universität Berlin)
Locke, Frederick L (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))
von Bergwelt-Baildon, Michael (Ludwig-Maximilians-University Hospital)
Mackensen, Andreas (Friedrich-Alexander-Universität Erlangen-Nürnberg)
Bethge, Wolfgang (University Hospital of Tübingen (Alemanya))
Barba, Pere (Vall d'Hebron Institut d'Oncologia)
Jain, Michael D (Moffitt Cancer Center (Tampa, Estats Units d'Amèrica))
Subklewe, Marion (Ludwig-Maximilians-University Hospital)
Universitat Autònoma de Barcelona. Departament de Medicina

Date:	2022
Abstract:	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. 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. 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). 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.
Note:	Altres ajuts: a Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) research grant provided within the Sonderforschungbereich SFB-TRR 388/1 2021-452881907, and DFG research grant 451580403 (to MS)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Journal for immunotherapy of cancer, Vol. 10, Num. 5 (may 2022) , ISSN 2051-1426

DOI: 10.1136/jitc-2021-004475
PMID: 35580927

14 p, 5.0 MB

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