{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:44:17Z","timestamp":1785725057938,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Bortezomib, a proteasome inhibitor, is one of the key agents in the first-line treatment of multiple myeloma (MM). Although its hepatotoxic potential has been described in case reports and registration trials, systematic real-life studies quantifying the incidence, dynamics and prognostic significance of liver injury during bortezomib-based therapy are lacking. We aimed to characterize the hepatotoxicity profile of first-line bortezomib-based regimens. Methods: We retrospectively analyzed 115 consecutively treated MM patients at University Hospital Dubrava (2016\u20132023) who received first-line bortezomib-based regimens (VCD, VD, VMP, VRD, VTD). Liver function parameters (bilirubin, albumin, AST, ALT, GGT, ALP) were recorded at baseline and after 1 and 3 months, and abnormalities were graded according to CTCAE v5.0. Predictors of liver injury and its association with IMWG response and overall survival (OS) were assessed. Results: Elevation of any liver transaminase was observed in 33% of patients at baseline, 40.2% at 1 month and 24% at 3 months. De novo worsening developed in 23.4% of patients, predominantly (88%) within the first month, with a dominantly cholestatic pattern (96%). Liver injury was not associated with the antimyeloma regimen, the class of supportive therapy, or most comorbidities (besides second malignancy for 3-month derangement), whereas higher tumor burden and baseline liver injury were identified among the predictors. Transaminase abnormalities were not associated with the likelihood of achieving a response, but liver injury at 3 months independently predicted shorter OS (HR 2.83; p = 0.011) after adjustment for age, sex and ISS stage. Conclusions: Liver injury in bortezomib-treated MM patients is frequent and predominantly associated with the biology of the underlying disease rather than necessarily with the antimyeloma therapy itself; abnormalities persisting at 3 months deserve attention as an independent adverse prognostic marker.<\/jats:p>","DOI":"10.3390\/ph19081205","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatotoxicity Profile of Bortezomib-Containing Regimens for First-Line Multiple Myeloma Treatment"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-2040","authenticated-orcid":false,"given":"Marko","family":"Lucijanic","sequence":"first","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, Salata 3, 10000 Zagreb, Croatia"},{"name":"Scientific Research and Translational Medicine Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerko","family":"Orec","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Zagreb, Salata 3, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ena","family":"Soric","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anica","family":"Sabljic","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeljko","family":"Jonjic","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Pirsic","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozren","family":"Jaksic","sequence":"additional","affiliation":[{"name":"Hematology Department, University Hospital Dubrava, Avenija Gojka Suska 6, 10000 Zagreb, Croatia"},{"name":"School of Medicine, University of Zagreb, Salata 3, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. 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