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      A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma

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      1 , 2 , , 3 , 4 , 1 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 6 , 27 , 28 , 4 , 5 , 7 , 29
      Nature Medicine
      Nature Publishing Group US
      Outcomes research, B-cell lymphoma, Cancer immunotherapy

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          Abstract

          Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298). After 1:1 propensity score matching ( n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively ( P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46–0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45–0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1–2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1–2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL.

          Abstract

          Analysis of outcomes of over 800 patients with relapsed/refractory diffuse large B cell lymphoma, treated with commercially available CAR T cell therapy, supports higher efficacy and also a higher toxicity of axicabtagene ciloleucel compared to tisagenlecleucel as the third or more treatment line for this type of tumor.

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          Most cited references35

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          Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

          In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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            Sensitivity Analysis in Observational Research: Introducing the E-Value.

            Sensitivity analysis is useful in assessing how robust an association is to potential unmeasured or uncontrolled confounding. This article introduces a new measure called the "E-value," which is related to the evidence for causality in observational studies that are potentially subject to confounding. The E-value is defined as the minimum strength of association, on the risk ratio scale, that an unmeasured confounder would need to have with both the treatment and the outcome to fully explain away a specific treatment-outcome association, conditional on the measured covariates. A large E-value implies that considerable unmeasured confounding would be needed to explain away an effect estimate. A small E-value implies little unmeasured confounding would be needed to explain away an effect estimate. The authors propose that in all observational studies intended to produce evidence for causality, the E-value be reported or some other sensitivity analysis be used. They suggest calculating the E-value for both the observed association estimate (after adjustments for measured confounders) and the limit of the confidence interval closest to the null. If this were to become standard practice, the ability of the scientific community to assess evidence from observational studies would improve considerably, and ultimately, science would be strengthened.
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              Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

              Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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                Author and article information

                Contributors
                emmanuel.bachy@chu-lyon.fr
                Journal
                Nat Med
                Nat Med
                Nature Medicine
                Nature Publishing Group US (New York )
                1078-8956
                1546-170X
                22 September 2022
                22 September 2022
                2022
                : 28
                : 10
                : 2145-2154
                Affiliations
                [1 ]GRID grid.413852.9, ISNI 0000 0001 2163 3825, Hematology Department, , Hospices Civils de Lyon, Pierre Bénite, ; Lyon, France
                [2 ]GRID grid.462394.e, ISNI 0000 0004 0450 6033, International Center for Infectiology Research (CIRI), Inserm U1111, ; Lyon, France
                [3 ]GRID grid.418596.7, ISNI 0000 0004 0639 6384, Hematology Department, , Institut Curie, ; Paris, France
                [4 ]GRID grid.413328.f, ISNI 0000 0001 2300 6614, Hematology Department, , Hôpital Saint Louis, ; Paris, France
                [5 ]GRID grid.411154.4, ISNI 0000 0001 2175 0984, Hematology Department, , CHU de Rennes, ; Rennes, France
                [6 ]GRID grid.157868.5, ISNI 0000 0000 9961 060X, Hematology Department, , CHU de Montpellier & UMR-CNRS, ; Montpellier, France
                [7 ]GRID grid.410463.4, ISNI 0000 0004 0471 8845, Hematology Department, , CHU de Lille, ; Lille, France
                [8 ]GRID grid.412116.1, ISNI 0000 0001 2292 1474, Hematology Department, , Hôpital Henri Mondor, ; Créteil, France
                [9 ]GRID grid.42399.35, ISNI 0000 0004 0593 7118, Hematology Department, , CHU de Bordeaux, ; Bordeaux, France
                [10 ]GRID grid.410527.5, ISNI 0000 0004 1765 1301, Hematology Department, , CHU de Nancy, ; Nancy, France
                [11 ]GRID grid.411175.7, ISNI 0000 0001 1457 2980, Hematology Department, , CHU de Toulouse, ; Toulouse, France
                [12 ]GRID grid.411163.0, ISNI 0000 0004 0639 4151, Hematology Department, , CHU de Clermont Ferrand, ; Clermont-Ferrand, France
                [13 ]GRID grid.14925.3b, ISNI 0000 0001 2284 9388, Hematology Department, , Gustave Roussy Cancer Campus, Villejuif, ; Paris, France
                [14 ]GRID grid.411439.a, ISNI 0000 0001 2150 9058, Hematology Department, , Hôpital de la Pitié Salpêtrière & AP-HP Sorbonne Université, ; Paris, France
                [15 ]GRID grid.31151.37, Hematology Department, , CHU de Dijon, ; Dijon, France
                [16 ]GRID grid.412370.3, ISNI 0000 0004 1937 1100, Hematology Department, , Hôpital Saint Antoine & Sorbonne University & Inserm UMRs 938, ; Paris, France
                [17 ]GRID grid.411162.1, ISNI 0000 0000 9336 4276, Hematology Department, , CHU de Poitiers, ; Poitiers, France
                [18 ]GRID grid.134996.0, ISNI 0000 0004 0593 702X, Hematology Department, , CHU d’Amiens, ; Amiens, France
                [19 ]GRID grid.410528.a, ISNI 0000 0001 2322 4179, Hematology Department, , CHU de Nice, ; Nice, France
                [20 ]GRID grid.418110.d, ISNI 0000 0004 0642 0153, Hematology Department, , CHU de Grenoble & University Grenoble-Alpes, Institute for Advanced Biosciences, ; La Tronche, France
                [21 ]GRID grid.411178.a, ISNI 0000 0001 1486 4131, Hematology Department, , CHU de Limoges, ; Limoges, France
                [22 ]GRID grid.411158.8, ISNI 0000 0004 0638 9213, Hematology Department, , CHU de Besançon, ; Besançon, France
                [23 ]GRID grid.411167.4, ISNI 0000 0004 1765 1600, Hematology Department, , CHU de Tours, ; Tours, France
                [24 ]GRID grid.411784.f, ISNI 0000 0001 0274 3893, Hematology Department, , Hôpital Cochin, ; Paris, France
                [25 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Hematology Department, , Hôpital Necker, ; Paris, France
                [26 ]GRID grid.277151.7, ISNI 0000 0004 0472 0371, Hematology Department, , CHU de Nantes, ; Nantes, France
                [27 ]GRID grid.488249.b, Biostatistics Department, , LYSARC, ; Lyon, France
                [28 ]GRID grid.488249.b, Medical and Scientific Affairs Department, , LYSARC, ; Lyon, France
                [29 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, Lille University, , ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, ; Lille, France
                Author information
                http://orcid.org/0000-0003-2694-7510
                http://orcid.org/0000-0003-1866-828X
                http://orcid.org/0000-0002-7791-0470
                http://orcid.org/0000-0002-4460-5939
                http://orcid.org/0000-0003-4879-8106
                http://orcid.org/0000-0002-9941-2448
                Article
                1969
                10.1038/s41591-022-01969-y
                9556323
                36138152
                86723395-af8b-4c71-967e-6eed801c768f
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 29 March 2022
                : 26 July 2022
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                © The Author(s), under exclusive licence to Springer Nature America, Inc. 2022

                Medicine
                outcomes research,b-cell lymphoma,cancer immunotherapy
                Medicine
                outcomes research, b-cell lymphoma, cancer immunotherapy

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