Citation: Rentsch, V.; Seipel, K.; Banz, Y.; Wiedemann, G.; Porret, N.; Bacher, U.; Pabst, T. Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy. Cancers 2022, 14, 2516. https://doi.org/10.3390/ cancers14102516 Academic Editor: Vita Golubovskaya Received: 26 April 2022 Accepted: 18 May 2022 Published: 20 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article Glofitamab Treatment in Relapsed or Refractory DLBCL after CAR T-Cell Therapy Vera Rentsch 1 , Katja Seipel 2 , Yara Banz 3 , Gertrud Wiedemann 4 , Naomi Porret 4 , Ulrike Bacher 5 and Thomas Pabst 1, * 1 Department of Medical Oncology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland; vera.rentsch@students.unibe.ch 2 Department of Biomedical Research, University of Bern, 3008 Bern, Switzerland; katja.seipel@dbmr.unibe.ch 3 Institute of Pathology, Inselspital, University of Bern, 3008 Bern, Switzerland; yara.banz@pathology.unibe.ch 4 Center of Laboratory Medicine (ZLM), Inselspital, Bern University Hospital, 3010 Bern, Switzerland; gertrud.wiedemann@insel.ch (G.W.); naomiazur.porret@insel.ch (N.P.) 5 Department of Hematology, Inselspital, Bern University Hospital, 3010 Bern, Switzerland; veraulrike.bacher@insel.ch * Correspondence: thomas.pabst@insel.ch; Tel.: +41-31-632-8430; Fax: +41-31-632-3410 Simple Summary: CAR T-cell therapies represent a major advance in the treatment of relapsed B-cell non-Hodgkin lymphomas. Nevertheless, a significant proportion of these patients will experience disease progression following CAR T treatment. For these patients, no standard therapeutic procedure is established so far. The novel bispecific antibody glofitamab has shown promising activity in the treatment of refractory or relapsed B-cell non-Hodgkin lymphomas. In this study, we provide evidence for good tolerance and promising efficacy of glofitamab administration in patients relapsing after CAR T-cell therapy. Abstract: Chimeric antigen receptor T-cells (CAR T) treatment has become a standard option for patients with diffuse large B-cell lymphomas (DLBCL), which are refractory or relapse after two prior lines of therapy. However, little evidence exists for treatment recommendations in patients who relapse after CAR T-cell treatment and the outcome for such patients is poor. In this study, we evaluated the safety and efficacy of a monotherapy with the bispecific CD20xCD3 antibody glofitamab in patients who progressed after CAR T treatment. We report nine consecutive patients with progressive DLBCL after preceding CAR T-cell therapy. The patients received a maximum of 12 cycles of glofitamab after a single obinutuzumab pre-treatment at an academic institution. CRS was observed in two patients (grade 2 in both patients). We observed an overall response rate of 67%, with four patients achieving a complete response and a partial remission in two patients. Interestingly, we identified increased persistence of circulating CAR T-cells in peripheral blood in three of the five patients with measurable CAR T-cells. Our data suggest that glofitamab treatment is well tolerated and effective in patients with DLBCL relapsing after CAR T-cell therapy and can enhance residual CAR T-cell activity. Keywords: CAR T-cell therapy; glofitamab; diffuse large B-cell lymphoma (DLBCL); relapse 1. Introduction The most common type of aggressive non-Hodgkin Lymphomas is diffuse large B-cell lymphoma (DLBCL) [1]. Whereas most patients achieve a complete remission following first-line therapy with chemotherapy and rituximab, approximately 40% will, ultimately, relapse [2,3]. Such patients usually undergo salvage therapy, with a proportion of 30–40% of them responding [4,5], and these patients are candidates for consolidation with autologous stem cell transplantation (ASCT). Among them, up to 50% may relapse after ASCT [6–8]. For DLBCL patients who relapse or are refractory after at least two lines Cancers 2022, 14, 2516. https://doi.org/10.3390/cancers14102516 https://www.mdpi.com/journal/cancers