@article{LiebersDuellFitzgeraldetal.2021, author = {Liebers, Nora and Duell, Johannes and Fitzgerald, Donnacha and Kerkhoff, Andrea and Noerenberg, Daniel and Kaebisch, Eva and Acker, Fabian and Fuhrmann, Stephan and Leng, Corinna and Welslau, Manfred and Chemnitz, Jens and Middeke, Jan-Moritz and Weber, Thomas and Holtick, Udo and Trappe, Ralf and Pfannes, Roald and Liersch, Ruediger and Spoer, Christian and Fuxius, Stefan and Gebauer, Niklas and Caill{\´e}, L{\´e}andra and Geer, Thomas and Koenecke, Christian and Keller, Ulrich and Claus, Rainer and Mougiakakos, Dimitrios and Mayer, Stephanie and Huettmann, Andreas and Pott, Christiane and Trummer, Arne and Wulf, Gerald and Brunnberg, Uta and Bullinger, Lars and Hess, Georg and Mueller-Tidow, Carsten and Glass, Bertram and Lenz, Georg and Dreger, Peter and Dietrich, Sascha}, title = {Polatuzumab vedotin as a salvage and bridging treatment in relapsed or refractory large B-cell lymphomas}, series = {Blood Advances}, volume = {5}, journal = {Blood Advances}, doi = {10.1182/bloodadvances.2020004155}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369173}, pages = {2707-2716}, year = {2021}, abstract = {The antibody-drug conjugate polatuzumab vedotin (pola) has recently been approved in combination with bendamustine and rituximab (pola-BR) for patients with refractory or relapsed (r/r) large B-cell lymphoma (LBCL). To investigate the efficacy of pola-BR in a real-world setting, we retrospectively analyzed 105 patients with LBCL who were treated in 26 German centers under the national compassionate use program. Fifty-four patients received pola as a salvage treatment and 51 patients were treated with pola with the intention to bridge to chimeric antigen receptor (CAR) T-cell therapy (n = 41) or allogeneic hematopoietic cell transplantation (n = 10). Notably, patients in the salvage and bridging cohort had received a median of 3 prior treatment lines. In the salvage cohort, the best overall response rate was 48.1\%. The 6-month progression-free survival and overall survival (OS) was 27.7\% and 49.6\%, respectively. In the bridging cohort, 51.2\% of patients could be successfully bridged with pola to the intended CAR T-cell therapy. The combination of pola bridging and successful CAR T-cell therapy resulted in a 6-month OS of 77.9\% calculated from pola initiation. Pola vedotin-rituximab without a chemotherapy backbone demonstrated encouraging overall response rates up to 40\%, highlighting both an appropriate alternative for patients unsuitable for chemotherapy and a new treatment option for bridging before leukapheresis in patients intended for CAR T-cell therapy. Furthermore, 7 of 12 patients with previous failure of CAR T-cell therapy responded to a pola-containing regimen. These findings suggest that pola may serve as effective salvage and bridging treatment of r/r LBCL patients.}, language = {en} } @article{LenzPahlHaucketal.2021, author = {Lenz, Dominic and Pahl, Jens and Hauck, Fabian and Alameer, Seham and Balasubramanian, Meena and Baric, Ivo and Boy, Nikolas and Church, Joseph A. and Crushell, Ellen and Dick, Anke and Distelmaier, Felix and Gujar, Jidnyasa and Indolfi, Giuseppe and Lurz, Eberhard and Peters, Bianca and Schwerd, Tobias and Serranti, Daniele and K{\"o}lker, Stefan and Klein, Christoph and Hoffmann, Georg F. and Prokisch, Holger and Greil, Johann and Cerwenka, Adelheid and Giese, Thomas and Staufner, Christian}, title = {NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency}, series = {Journal of Clinical Immunology}, volume = {41}, journal = {Journal of Clinical Immunology}, number = {8}, issn = {0271-9142}, doi = {10.1007/s10875-021-01110-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308362}, pages = {1781-1793}, year = {2021}, abstract = {Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell-intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of na{\"i}ve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.}, language = {en} } @article{LoscherLoehleinLenz2021, author = {Loscher, Georg and L{\"o}hlein, Lukas and Lenz, Hansrudi}, title = {Dual Roles and Blurred Identities: A Framing Contest between Professional Associations in a Local Strategic Action Field}, series = {European Accounting Review}, volume = {30}, journal = {European Accounting Review}, doi = {10.1080/09638180.2021.1882319}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369504}, pages = {503-529}, year = {2021}, abstract = {This paper examines professional associations' local responses to global demands of accounting standardisation. Our longitudinal study from 1998 to 2018 analyses how professional associations of the German audit profession engaged in an intense framing contest over the adoption of external quality controls. Drawing on the concept of strategic action field and the literature on framing, we unpack how the gap between large audit firms and small audit firms increasingly undermined the capacity of the professional associations to fulfil their dual role of governance and representation. We unveil how their failed attempt to maintain the image of an unified profession ultimately led to the creation of a new professional association representing the 'small auditor' professional, which successfully, albeit temporarily, took control over the field of German auditing. Our findings suggest that the passivity of small audit firms in the process of translating global regulatory regimes should not be presumed. Rather, we provide insight into how small audit firms can rebuild their own identity by actively responding to waves of global regulation. Doing so, and contrary to prior research, our case highlights that governance units within strategic action fields are not necessarily aligned with the interests of the most powerful field actors.}, language = {en} }