{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:23:10Z","timestamp":1783686190217,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Relapsed\/refractory (R\/R) B-cell non-Hodgkin lymphomas (B-NHLs) remain a major therapeutic challenge, particularly in patients with aggressive subtypes and limited treatment options after multiple lines of therapy. The ViPOR regimen, a multi-targeted combination of venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide, has demonstrated promising activity in early-phase studies; however, real-world data are limited. Methods: We conducted a retrospective, two-center study including patients with R\/R B-NHL treated with the ViPOR regimen between January 2024 and April 2026. Clinical characteristics, treatment responses, survival outcomes, and safety data were analyzed. Results: A total of 14 patients were included, with a median age of 45 years and a median of 3.5 prior lines of therapy. Most patients had advanced-stage disease (71% stage IV), and 36% had primary refractory disease. The interim overall response rate (ORR) was 62%, including 31% complete response (CR) and 31% partial response. At the end of treatment, the ORR was 54%, with a CR rate of 54%. Radiotherapy was incorporated in selected patients with residual disease and contributed to response deepening. Six patients (43%) were successfully bridged to allogeneic stem cell transplantation, all in CR. Responses were notably more favorable in the activated B-cell (ABC) subtype compared to the germinal center subtype. The most common adverse events were neutropenia (57%) and diarrhea (36%), and the regimen demonstrated a manageable safety profile. During follow-up, 57% of patients remained alive. Conclusions: The ViPOR regimen demonstrated promising efficacy and acceptable safety in heavily pretreated R\/R B-NHL, particularly in the ABC subtype. Its ability to induce deep responses and enable bridging to allogeneic stem cell transplantation highlights its potential role in real-world clinical practice. Larger prospective studies are warranted to confirm these findings.<\/jats:p>","DOI":"10.3390\/jcm15145401","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:43:34Z","timestamp":1783683814000},"page":"5401","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Multi-Targeted Strategy for Relapsed\/Refractory B-Cell Non-Hodgkin Lymphoma: Real-World Outcomes of the ViPOR Regimen"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-8068","authenticated-orcid":false,"given":"S\u00fcreyya","family":"Yi\u011fit Kaya","sequence":"first","affiliation":[{"name":"Department of Hematology, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5191-174X","authenticated-orcid":false,"given":"Mehrad","family":"Vatani","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4766-1861","authenticated-orcid":false,"given":"Senem","family":"Maral","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1237-8281","authenticated-orcid":false,"given":"H\u00fcseyin Saffet","family":"Bek\u00f6z","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7053-0013","authenticated-orcid":false,"given":"Amir Hossein","family":"Abedi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-5797","authenticated-orcid":false,"given":"Olgu Erkin","family":"\u00c7\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-5571","authenticated-orcid":false,"given":"Beyza","family":"Oluk","sequence":"additional","affiliation":[{"name":"Department of Hematology, Kocaeli City Hospital, 41060 Kocaeli, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2035-9462","authenticated-orcid":false,"given":"Leylag\u00fcl","family":"Kaynar","sequence":"additional","affiliation":[{"name":"Department of Hematology, Medipol Mega University Hospital, Istanbul Medipol University, 34214 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1016\/S0140-6736(23)02705-8","article-title":"B-cell non-Hodgkin lymphomas","volume":"403","author":"Silkenstedt","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1182\/blood-2017-03-769620","article-title":"Outcomes in refractory diffuse large B-cell lymphoma: Results from the international SCHOLAR-1 study","volume":"130","author":"Crump","year":"2017","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6443","DOI":"10.1182\/blood-2024-203238","article-title":"A Systematic Literature Review of Clinical Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated in the Third-Line or Later Setting","volume":"144","author":"Bandy","year":"2024","journal-title":"Blood"},{"key":"ref_4","first-page":"2186","article-title":"Autologous stem cell transplant in fit patients with refractory or early relapsed diffuse large B-cell lymphoma that responded to salvage chemotherapy","volume":"109","author":"Tun","year":"2024","journal-title":"Haematologica"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1182\/blood.2022016945","article-title":"Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: A DESCAR-T analysis","volume":"140","author":"Bachy","year":"2022","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Profit\u00f3s-Pelej\u00e0, N., Santos, J.C., Mar\u00edn-Niebla, A., Rou\u00e9, G., and Ribeiro, M.L. (2022). Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas. Cancers, 14.","DOI":"10.3390\/cancers14040860"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ondrisova, L., and Mraz, M. (2020). Genetic and Non-Genetic Mechanisms of Resistance to BCR Signaling Inhibitors in B Cell Malignancies. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.591577"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1056\/NEJMoa2401532","article-title":"Combination Targeted Therapy in Relapsed Diffuse Large B-Cell Lymphoma","volume":"390","author":"Melani","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1182\/blood-2025-3688","article-title":"Efficacy and safety of vipor (P) in relapsed or refractory large B-cell lymphoma","volume":"146","author":"Oellerich","year":"2025","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1182\/blood-2024-200002","article-title":"Real-World Evidence of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, Lenalidomide with or without Polatuzumab (VIPOR(P)) for Relapsed\/Refractory Large B-Cell Lymphoma","volume":"144","author":"Kouidri","year":"2024","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1182\/blood-2024-194482","article-title":"A Pilot Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide (VIPOR) for Diffuse Large B-Cell Lymphoma Involving the Central Nervous System","volume":"144","author":"Dalela","year":"2024","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1182\/blood-2003-05-1545","article-title":"Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray","volume":"103","author":"Hans","year":"2004","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1182\/blood.V120.21.686.686","article-title":"The Bruton\u2019s Tyrosine Kinase (BTK) Inhibitor, Ibrutinib (PCI-32765), Has Preferential Activity in the ABC Subtype of Relapsed\/Refractory De Novo Diffuse Large B-Cell Lymphoma (DLBCL): Interim Results of a Multicenter, Open-Label, Phase 2 Study","volume":"120","author":"Wilson","year":"2012","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/nm.3884","article-title":"Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma","volume":"21","author":"Wilson","year":"2015","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1182\/blood.V118.21.4969.4969","article-title":"The Bruton\u2019s Tyrosine Kinase (BTK) Inhibitor PCI-32765 Inhibits Growth of ABC DLBCL Tumors In Vivo and in Vitro by Preventing Activation of Pro-Survival NF-\u03baB pathways","volume":"118","author":"Balasubramanian","year":"2011","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1038\/s41375-021-01470-4","article-title":"Inhibitors of Bcl-2 and Bruton\u2019s tyrosine kinase synergize to abrogate diffuse large B-cell lymphoma growth in vitro and in orthotopic xenotransplantation models","volume":"36","author":"Bertram","year":"2022","journal-title":"Leukemia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e006113","DOI":"10.1136\/jitc-2022-006113","article-title":"Venetoclax improves CD20 immunotherapy in a mouse model of MYC\/BCL2 double-expressor diffuse large B-cell lymphoma","volume":"11","author":"Melchor","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ccr.2012.05.024","article-title":"Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma","volume":"21","author":"Yang","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1111\/bjh.12172","article-title":"Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF 4 and cereblon expression","volume":"160","author":"Zhang","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1182\/blood-2023-174325","article-title":"Molecular Mechanism of Action of Glucocorticoids in Lymphoma Therapy","volume":"142","author":"Choi","year":"2023","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1182\/blood-2019-128704","article-title":"Rituximab and Obinutuzumab Induce Direct B-Cell Death Via B-Cell Receptor (BCR) Signaling, but Rituximab Elicits Stronger BCR-Derived Pro-Survival Signals Diminishing Apoptosis","volume":"134","author":"Edelmann","year":"2019","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1182\/blood-2019-125990","article-title":"Phase 1b Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed\/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis","volume":"134","author":"Melani","year":"2019","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1182\/blood-2020-141447","article-title":"Phase 1b\/2 Study of Vipor (Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide) in Relapsed\/Refractory B-Cell Lymphoma: Safety, Efficacy and Molecular Analysis","volume":"136","author":"Melani","year":"2020","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1182\/blood-2022-167887","article-title":"Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide (ViPOR) in Relapsed and Refractory Follicular Lymphoma: Analysis of Safety, Efficacy, and Minimal Residual Disease","volume":"140","author":"Melani","year":"2022","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1182\/blood-2023-180173","article-title":"Phase Ib\/II Study of Multi-Targeted Therapy with Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Lenalidomide (ViPOR) in Relapsed\/Refractory (R\/R) Diffuse Large B-Cell Lymphoma (DLBCL)","volume":"142","author":"Melani","year":"2023","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/hon.3164_437","article-title":"Venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide (ViPOR) in relapsed\/refractory (R\/R) and treatment-na\u00efve (TN) mantle cell lymphoma (MCL)","volume":"41","author":"Melani","year":"2023","journal-title":"Hematol. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e316_70094","DOI":"10.1002\/hon.70094_316","article-title":"316|MULTI-TARGETED THERAPY WITH VIPOR-P IN RELAPSED\/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: UPDATED ANALYSIS OF EFFICACY AND MINIMAL RESIDUAL DISEASE","volume":"43","author":"Melani","year":"2025","journal-title":"Hematol. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5401\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:06:47Z","timestamp":1783685207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":27,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145401"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145401","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}