GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany

Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, Ayuk F, Wagner-Drouet EM, Wulf GG, Marks R, Penack O, Schnetzke U, Koenecke C, von Bonin M, Stelljes M, Glass B, Baldus CD, Vucinic V, Mougiakakos D, Topp M, Fante MA, Schroers R, Bayir L, Borchmann P, Buecklein V, Hasenkamp J, Hanoun C, Thomas S, Beelen DW, Lengerke C, Kroeger N, Dreger P (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 140

Pages Range: 349-358

Journal Issue: 4

DOI: 10.1182/blood.2021015209

Abstract

CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC CAR T-cell therapies with the aim to explore risk factors associated with outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry for Stem Cell Transplantation (DRST) were eligible. The main outcomes analyzed were toxicities, response, overall survival (OS), and progression-free survival (PFS). We report 356 patients who received axi-cel (n = 173) or tisa-cel (n = 183) between November 2018 and April 2021 at 21 German centers. Whereas the axi-cel and tisa-cel cohorts were comparable for age, sex, lactate dehydrogenase (LDH), international prognostic index (IPI), and pretreatment, the tisa-cel group comprised significantly more patients with poor performance status, ineligibility for ZUMA-1, and the need for bridging, respectively. With a median follow-up of 11 months, Kaplan-Meier estimates of OS, PFS, and nonrelapse mortality (NRM) 12 months after dosing were 52%, 30%, and 6%, respectively. While NRM was largely driven by infections subsequent to prolonged neutropenia and/or severe neurotoxicity and significantly higher with axi-cel, significant risk factors for PFS on the multivariate analysis included bridging failure, elevated LDH, age, and tisa-cel use. In conclusion, this study suggests that important outcome determinants of CD19-directed CAR T-cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR T-cell therapy strategies.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Tübingen Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Köln Germany (DE) Klinikum der Universität München Germany (DE) Universitätsklinikum Essen Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz Germany (DE) Universitätsklinikum Göttingen Germany (DE) Universitätsklinikum Freiburg Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Jena Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Münster Germany (DE) HELIOS Kliniken Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Leipzig Germany (DE) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Regensburg Germany (DE) Universitätsklinikum Knappschaftskrankenhaus Bochum Germany (DE)

How to cite

APA:

Bethge, W.A., Martus, P., Schmitt, M., Holtick, U., Subklewe, M., von Tresckow, B.,... Dreger, P. (2022). GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. Blood, 140(4), 349-358. https://doi.org/10.1182/blood.2021015209

MLA:

Bethge, Wolfgang A., et al. "GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany." Blood 140.4 (2022): 349-358.

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