{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:25:35Z","timestamp":1788362735484,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014471","name":"Mundipharma Research Limited","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014471","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first\u2010line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open\u2010label, two\u2010stage trial investigating the safety and efficacy of tinostamustine in patients \u2265 18\u00a0years with relapsed\/refractory (R\/R) hematological malignancies, including HL. Stage 1 involved dose\u2010escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R\/R hematological malignancies. Ten patients with heavily pre\u2010treated HL entered dose\u2010escalation, with nine patients experiencing treatment\u2010emergent adverse events (TEAEs) considered to be related to study treatment\u2014primarily hematological toxicities. MTD was 100\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      tinostamustine over 60\u00a0min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced \u2265 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine\u2010related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression\u2010free survival 3.8\u00a0months (95% CI: 2.2\u20139.4\u00a0months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R\/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      ClinicalTrials.gov identifier: NCT02576496\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hon.70000","type":"journal-article","created":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T23:08:39Z","timestamp":1733094519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed\/Refractory Hodgkin Lymphoma From a Phase I Trial"],"prefix":"10.1002","volume":"43","author":[{"given":"Anna","family":"Sureda","sequence":"first","affiliation":[{"name":"Clinical Hematology Department Institut Catal\u00e0 d'Oncologia\u2010L\u2019Hospitalet de Llobregat IDIBELL Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-9026","authenticated-orcid":false,"given":"Antonio","family":"Pinto","sequence":"additional","affiliation":[{"name":"Hematology\u2010Oncology and Stem Cell Transplantation Unit Istituto Nazionale Tumori IRCCS\u2010Fondazione 'G. 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