Polatuzumab Vedotin in Relapsed and Refractory (r/r) Large B-Cell Lymphoma (LBCL): Real-World Data of the German National Compassionate Use Program (CUP)

Liebers, Nora

Oral and Poster Abstracts
627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Retrospective/Observational Studies: Poster I

Diseases, DLBCL, B-Cell Lymphoma, Lymphoid Malignancies, Clinically relevant

Nora Liebers, MD^1,2^*, Johannes Duell, MD³^*, Daniel Nörenberg, MD⁴^*, Eva Kaebisch, MD⁴^*, Andrea Kerkhoff, MD⁵^*, Fabian Acker, MD⁶^*, Stephan Fuhrmann, MD⁷^*, Corinna Leng, MD, PhD⁸^*, Manfred Welslau, MD⁹^*, Jens Chemnitz, MD¹⁰^*, Jan Moritz Middeke, MD¹¹^*, Thomas Weber, MD¹²^*, Ralf Ulrich Trappe, MD¹³^*, Roald Pfannes, MD¹⁴^*, Ruediger Liersch, MD¹⁵^*, Christian Spoer, MD¹⁶^*, Niklas Gebauer, MD¹⁷^*, Stefan Fuxius, MD¹⁸^*, Léandra Caillé¹^*, Christiane Pott, MD, PhD¹⁹^*, Christian Koenecke, MD²⁰^*, Udo Holtick²¹^*, Thomas Geer, MD²²^*, Ulrich Keller, MD⁸^*, Rainer Claus, MD²³^*, Dimitrios Mougiakakos, MD²⁴^*, Stephanie Mayer, MD²⁵^*, Andreas Hüttmann, MD²⁶, Arne Trummer, MD²⁷^*, Gerald Wulf, MD²⁸^*, Uta Brunnberg, MD⁶^*, Lars Bullinger, MD²⁹, Georg Hess, MD³⁰^*, Carsten Mueller-Tidow, MD^1,2^*, Bertram Glass, MD⁷^*, Georg Lenz³¹, Peter Dreger, MD¹ and Sascha Dietrich, M.D.^1,2,32

¹Internal Medicine V - Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
²National Center for Tumor Diseases Heidelberg, Heidelberg, Germany
³Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
⁴Department of Hematology, Oncology and Tumor Immunology (Campus Virchow-Klinikum), Charité University Medicine, Berlin, Germany
⁵Department of Medicine A, University Hospital Muenster, Muenster, Germany
⁶Department of Medicine 2, Hematology and Oncology, University Hospital Frankfurt, Frankfurt, Germany
⁷Department of Hematology, HELIOS Klinikum Berlin-Buch, Berlin, Germany
⁸Department of Hematology, Oncology, and Tumor Immunology (Campus Benjamin Franklin), Charité University Medicine, Berlin, Germany
⁹MVZ am Klinikum Aschaffenburg, Onkologie und Hämatologie, Aschaffenburg, Germany
¹⁰Gemeinschaftsklinikum Mittelrhein GmbH, Koblenz, Germany
¹¹University Hospital Dresden, Dresden, Germany
¹²Department of Medicine IV, Hematology and Oncology, University Hospital Halle, Halle, DEU
¹³Department of Hematology and Oncology, DIAKO Hospital Bremen, Bremen, Germany
¹⁴Department of Medicine I, Städtisches Klinikum Dessau, Dessau, Germany
¹⁵Gemeinschaftspraxis für Hämatologie und Onkologie, Muenster, Germany
¹⁶MVZ am EVK Düsseldorf, Internistische Onkologie und Hämatologie, Düsseldorf, Germany
¹⁷Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
¹⁸Onkologische Schwerpunktpraxis Heidelberg, Heidelberg, Germany
¹⁹Second Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
²⁰Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
²¹Department of Internal Medicine I, Leukapheresis and Stem Cell Transplant Unit, University Hospital of Cologne, Cologne, Germany
²²Diakonie Klinikum Schwäbisch-Hall, Innere Medizin III, Schwäbisch-Hall, Germany
²³Hematology and Oncology, Medical Faculty, University of Augsburg, Augsburg, Germany
²⁴Department of Internal Medicine 5, Hematology and Oncology, University Hospital of Erlangen, Erlangen, Germany
²⁵Department of Internal Medicine III, University Hospital of Regensburg, Regensburg, Germany
²⁶Department of Hematology, University Hospital of Essen, Essen, Germany
²⁷Department of Hematology and Oncology, Klinikum Braunschweig, Braunschweig, Germany
²⁸Clinic for Hematology and Medical Oncology, University Medicine Göttingen, Goettingen, Germany
²⁹Department of Hematology, Oncology and Tumor Immunology, Charité University Medicine Berlin, Berlin, Germany
³⁰Department of Hematology, Medical Oncology and Pneumology, Johannes Gutenberg University of Mainz, Mainz, Germany
³¹Department of Medicine A, University Hospital Muenster, Munster, Germany
³²European Molecular Biology Laboratory (EMBL), Heidelberg, Germany

Introduction

The antibody-drug conjugate polatuzumab vedotin (Pola) has recently been approved in combination with bendamustine and rituximab (Pola-BR) for patients with r/r diffuse LBCL (DLBCL).

Methods

To characterize the efficacy of Pola-BR in a real-world setting, we retrospectively analyzed data from 97 patients with r/r LBCL who were treated with Pola in 24 German centers within the national CUP. Clinical baseline and follow-up (FU) data were collected by chart review and summarized descriptively. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier and Cox regression methods. Fisher’s exact test was used to compare categorical factors between groups of patients.

Results

97 patients with LBCL (DLBCL n=90, High-grade B-cell lymphoma n=6, Primary mediastinal B-cell lymphoma n=1) were included as of July 22^nd, 2020. 49 patients were treated with Pola as bridging concept to immunotherapies (bridging cohort: chimeric antigen receptor T-cells (CART) n=39, allogeneic stem cell transplantation (alloSCT) n=9, bispecific antibodies n=1), and 48 patients were treated with Pola in palliative intention (palliative cohort).

Within the bridging cohort the median age was 61 years (range: 22-82). Patients were heavily pretreated with a median of 3 treatment lines (range: 2-6). 84% (41/49 patients) had been refractory to their last treatment line, and 31% had failed an autologous stem cell transplantation. Notably, 14% and 10% of patients had failed prior CART and alloSCT, respectively, and were planned for the alternate cellular immunotherapy. Based on an individual decision, patients were treated with Pola-Rituximab (Pola-R, n=20), Pola-chemotherapy (Pola-chemo, BR n=25; R-CHP n=1) or Pola-monotherapy (Pola-mono, n=3). With a median of 2 Pola cycles (range 1-6), overall response rate (ORR) of all evaluable patients was 33% (15/46 patients) including patients with complete response (CR n=1), partial response (PR n=9) and clinical response (n=5). Although not significant, ORR tended to be better in patients treated with Pola-chemo versus Pola-R/Pola-mono (ORR: 42% versus 20%, Fishers test p=0.1). 11 of these 15 responders (24% of the entire bridging cohort) proceeded to CART or alloSCT, while 4 responders (8% of entire bridging cohort) experienced fast progression after their initial response and were referred to best supportive care. 15 of 31 non-responders (33% of entire bridging cohort) underwent immunotherapy with either stable disease (n=6), mixed response (n=2), or progression on Pola (n=7). The remaining 16 patients (35% of entire bridging cohort) were all refractory to Pola and either received alternative salvage treatments which enabled 8 further patients to proceed to the intended immunotherapy, or best supportive care. Taking the effects of CART or alloSCT into account, median OS from initiation of Pola treatment was 8.2 months (median FU 7.2 months, Fig. 1A).

The palliative cohort tended to be older than the bridging cohort with a median age of 73.5 years (range: 37-86, p<0.001). Patients were pretreated with a median of 3 treatment lines (range: 2-8), and 85% (41/48 patients) had been refractory to their last treatment line. Patients in the palliative cohort were treated with a median of 4 Pola cycles (range: 1-9). 65% received Pola-chemo (BR, n=30; R-Gemcitabine, n=1) and 35% Pola-R. The CR rate and ORR was 19% (9/48) and 56% (27/48), respectively. The 6-month PFS and OS from initiation of Pola was 36% and 51%, respectively (median FU of 9.7 months, Fig. 1B). Again, ORR and OS tended to be better in patients treated with Pola-chemo versus Pola-R (ORR: 61% versus 47%, Fishers test p=0.4; median OS 7.2 versus 4 months, HR 0.8, 95%CI 0.4-1.9, p=0.7). In univariate analysis, failure to respond to the last treatment line predicted inferior PFS (HR 2.4, 95%CI 1.2-5.0 p=0.02) and OS (HR 2.5, 95%CI 1.2-5.4 p=0.02). Patients with more than two prior treatment lines in total tended to have a shorter PFS (HR 2.0, 95% CI 0.9-4.5, p=0.1) and OS (HR 1.8, 95% CI 0.8-4.0, p=0.2), although significance was not reached.

Conclusion

Pola permits effective bridging to CART and alloSCT in r/r LBCL. In the palliative setting, Pola represents an effective salvage option for patients with transplantation-ineligible r/r LBCL. Compared to the approval study, the inferior outcome of the patients of this real-world analysis might be explained by their more advanced disease course.

Disclosures: Duell: Morphosys: Research Funding. Kerkhoff: BMS: Honoraria. Leng: Roche: Other: lecture fee; Celgene: Other: traveling expenses and congress attendance fee. Holtick: Miltenyi Biotec B.V. & Co. KG: Honoraria. Mayer: Amgen: Honoraria, Other: travel grants; Abbvie: Other: travel grants; Novartis: Honoraria; Roche: Honoraria. Hüttmann: Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Gilead: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Roche: Other: Travel expenses; Seattle Genetics: Research Funding; University Hospital Essen, University of Duisburg-Essen, Essen, Germany: Current Employment; Lead Discovery Center GmbH: Consultancy. Brunnberg: Gilead: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants; MSD: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Amgen: Other: Travel grants. Bullinger: Menarini: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Hexal: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Hess: Roche: Research Funding; Celgene: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genmab: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astra: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mueller-Tidow: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Deutsche Krebshilfe: Research Funding; BMBF: Research Funding; Wilhelm-Sander-Stiftung: Research Funding; Jose-Carreras-Siftung: Research Funding; Bayer AG: Research Funding; Daiichi Sankyo: Research Funding; BiolineRx: Research Funding; Janssen-Cilag Gmbh: Membership on an entity's Board of Directors or advisory committees; Deutsche Forschungsgemeinschaft: Research Funding. Lenz: Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy; AQUINOX: Research Funding; Agios: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Morphosys: Consultancy, Honoraria, Research Funding; BMS: Consultancy; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Verastem: Research Funding; Incyte: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Nanostring: Consultancy. Dreger: Roche: Consultancy, Speakers Bureau; Neovii: Research Funding; AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy; Gilead: Consultancy, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau. Dietrich: Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees.

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1206 Polatuzumab Vedotin in Relapsed and Refractory (r/r) Large B-Cell Lymphoma (LBCL): Real-World Data of the German National Compassionate Use Program (CUP)