{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:20:31Z","timestamp":1775218831035,"version":"3.50.1"},"reference-count":40,"publisher":"American Society of Hematology","issue":"15","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR\u2013human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed\/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF\/R-CHOP would be declared active if \u226512 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF\/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and\/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF\/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002270","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T16:31:25Z","timestamp":1596817885000},"page":"3648-3658","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":31,"title":["Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial"],"prefix":"10.1182","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-6124","authenticated-orcid":false,"given":"Andr\u00e9s J. 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and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Sassone","sequence":"additional","affiliation":[{"name":"Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piera","family":"Angelillo","sequence":"additional","affiliation":[{"name":"Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Guggiari","sequence":"additional","affiliation":[{"name":"Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Steffanoni","sequence":"additional","affiliation":[{"name":"Lymphoma Unit, Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute, Milan, 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