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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorRejeski, Kai
dc.contributor.authorPerez, Ariel
dc.contributor.authorIacoboni García-Calvo, Gloria Inés
dc.contributor.authorPenack, Olaf
dc.contributor.authorBücklein, Veit
dc.contributor.authorJentzsch, Liv
dc.contributor.authorCarpio Segura, Cecilia Carmen
dc.contributor.authorBarba Suñol, Pere
dc.date.accessioned2022-09-06T12:22:15Z
dc.date.available2022-09-06T12:22:15Z
dc.date.issued2022-05
dc.identifier.citationRejeski K, Perez A, Iacoboni G, Penack O, Bücklein V, Jentzsch L, et al. The CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL. J Immunother Cancer. 2022 May;10(5):e004475.
dc.identifier.issn2051-1426
dc.identifier.urihttp://hdl.handle.net/11351/8036
dc.descriptionHematologic neoplasms; Receptors; Chimeric antigen
dc.description.abstractBackground 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). HThigh 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 HThigh (16% vs 46%, p<0.001), but not HTlow patients (0% vs 2%, p=n.s.). Collectively, HThigh 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 HThigh 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.
dc.language.isoeng
dc.publisherBMJ
dc.relation.ispartofseriesJournal for ImmunoTherapy of Cancer;10(5)
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScientia
dc.subjectCèl·lules B - Tumors - Tractament
dc.subjectImmunoteràpia
dc.subjectAntígens CD - Immunologia
dc.subject.meshLymphoma, Large B-Cell, Diffuse
dc.subject.mesh/therapy
dc.subject.meshImmunotherapy, Adoptive
dc.subject.meshAntigens, CD19
dc.titleThe CAR-HEMATOTOX risk-stratifies patients for severe infections and disease progression after CD19 CAR-T in R/R LBCL
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1136/jitc-2021-004475
dc.subject.decslinfoma de células B grandes difuso
dc.subject.decs/terapia
dc.subject.decsinmunoterapia adoptiva
dc.subject.decsantígenos CD19
dc.relation.publishversionhttp://dx.doi.org/10.1136/jitc-2021-004475
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Rejeski K] Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany. Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany. German Cancer Consortium (DKTK) Munich Site, and German Cancer Research Center, Heidelberg, Germany. [Perez A] Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, Florida, USA. Blood & Marrow Transplant Program, Miami Cancer Institute, Miami, Florida, USA. [Iacoboni G, Carpio C, Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma of Barcelona, Bellaterra, Spain. [Penack O] Department of Hematology, Oncology and Tumorimmunology, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. German Cancer Consortium (DKTK) Berlin Site, and German Cancer Research Center, Heidelberg, Germany. [Bücklein V] Department of Medicine III, Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany. Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany. [Jentzsch L] Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany
dc.identifier.pmid35580927
dc.identifier.wos000797594100008
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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