{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T22:00:20Z","timestamp":1769810420510,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Roche Pharma AG and AbbVie Inc.","award":["ML40029"],"award-info":[{"award-number":["ML40029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Relapsed and refractory (rr) primary large B-cell lymphoma of the central nervous system (PCNSL) has a dismal prognosis, and the standard of care is not established. The most common genetic imbalance includes the B-cell lymphoma 2 (BCL-2) locus. Methods: We planned a bi-centric phase Ib dose-escalation study with the chemotherapy-free combination of the BCL-2 inhibitor venetoclax and CD20 antibody obinutuzumab for rrPCNSL patients in Germany. The intended treatment consisted of 6 cycles of fixed-dose obinutuzumab at 1000 mg intravenously every 3 weeks, and an oral daily dose of 600, 800, or 1000 mg venetoclax, depending on the planned dosing group, followed by a 12-month venetoclax maintenance period. The primary endpoint was the pharmacokinetics of venetoclax and obinutuzumab in cerebrospinal fluid (CSF). Results: This study was prematurely terminated after registration of 5\/15 (33%) patients in dosing group 1 (600 mg oral daily dose of venetoclax) between May 2020 and November 2021. The mean ratio of the concentration of venetoclax in CSF over peripheral blood was 0.55% (\u00b10.28 standard deviation (SD)) and 0.25% (\u00b10.23 SD) for obinutuzumab. Two of five patients achieved complete remission, and each one patient achieved partial remission and stable disease as best response. The median duration of response was 6.5 months (range 0.7\u201347). Conclusions: Venetoclax and obinutuzumab can penetrate into the central nervous system, but the CSF concentration did not correlate with the outcome. The combination is feasible, tolerable, and may lead to durable responses in selected rrPCNSL patients.<\/jats:p>","DOI":"10.3390\/cancers18030455","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T11:09:22Z","timestamp":1769771362000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Phase Ib VenObi CNS Study: Chemotherapy-Free Treatment with Venetoclax and Obinutuzumab for Relapsed\/Refractory Primary Large B-Cell Lymphoma of the Central Nervous System"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0088-1915","authenticated-orcid":false,"given":"Julia","family":"Wendler","sequence":"first","affiliation":[{"name":"Clinic of Hematology, Oncology, Stem Cell Transplantation and Palliative Care, Klinikum Stuttgart, 70174 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Kasenda","sequence":"additional","affiliation":[{"name":"Medical Oncology, University Hospital Basel, 4031 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2992-7868","authenticated-orcid":false,"given":"Eliza M.","family":"Lauer","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0175-9823","authenticated-orcid":false,"given":"Kudret","family":"Kama","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Oncology, Stem Cell Transplantation and Palliative Care, Klinikum Stuttgart, 70174 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9119-4589","authenticated-orcid":false,"given":"Lisa Kristina","family":"Isbell","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1639-8762","authenticated-orcid":false,"given":"Dominik","family":"Marschner","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Oncology, Stem Cell Transplantation and Palliative Care, Klinikum Stuttgart, 70174 Stuttgart, Germany"},{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florian","family":"Scherer","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Malenica","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cora","family":"Gloggengiesser","sequence":"additional","affiliation":[{"name":"Stuttgart Cancer Center\u2014Tumorzentrum Eva Mayr-Stihl, 70174 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elke","family":"Valk","sequence":"additional","affiliation":[{"name":"Stuttgart Cancer Center\u2014Tumorzentrum Eva Mayr-Stihl, 70174 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-2125","authenticated-orcid":false,"given":"Elisabeth","family":"Schorb","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Medical Center\u2014University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Illerhaus","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Oncology, Stem Cell Transplantation and Palliative Care, Klinikum Stuttgart, 70174 Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th Edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid 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