Hepatotoxicity Profile of Bortezomib-Containing Regimens for First-Line Multiple Myeloma Treatment

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 (2016-2023) 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.