Presenters: Grace Mosallam, PharmD Candidate Class of 2023, Massachusetts College of Pharmacy and Health Sciences, Boston, MA; Loriel J. Solodokin, PharmD, BCOP, Massachusetts College of Pharmacy and Health Sciences, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA
Co-Authors: Eric S. Winer, MD, Dana-Farber Cancer Institute; Julia Keating, MS, Dana-Farber Cancer Institute, Boston, MA
BACKGROUND: Sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is an often-fatal condition in patients who have had hematopoietic stem-cell transplant (HSCT). Gemtuzumab-ozogamicin (GO) and inotuzumab-ozogamicin (InO), 2 antibody–drug conjugates, are indicated for the management of acute leukemias and have black box warnings for SOS/VOD. Given the paucity of data on ursodiol’s use as SOS/VOD prophylaxis in patients who did not have HSCT, this study assessed the real-world comparative incidences of hepatotoxicity and SOS/VOD in adults with acute leukemia who received GO/InO and did or did not receive ursodiol prophylaxis.
OBJECTIVES: The primary objective was to assess the incidence of hepatotoxicity and SOS/VOD in patients who received ursodiol prophylaxis versus those who did not receive ursodiol prophylaxis. The secondary objective was to quantify the time to hepatotoxicity and confirmed SOS/VOD based on the receipt of ursodiol.
METHOD: In an Institutional Review Board–approved, multicenter, retrospective chart review of adults (aged ≥18 years) with leukemia who received ≥1 dose of GO/InO at the Harvard Cancer Centers between September 1, 2017, and September 1, 2021, the follow-up period was 100 days after the administration of GO/InO. Patients who received HSCT within the 100 days were excluded. The data collection points included anthropometrics; details on the primary malignancy before the HSCT, GO/InO, and ursodiol regimens; hepatic laboratory tests and hepatotoxic concomitant medications; SOS/VOD diagnostic findings; and overall survival. We implemented descriptive statistics and refined analyses via a 2-sided Wilcoxon rank-sum test, a 2-sided Fisher’s exact test, and a log-rank test.
RESULTS: Overall, 93 patients were analyzed. In all, 77.4% received ursodiol prophylaxis (26.4% of patients who received GO/73.6% of patients who received InO) and 21.8% did not (100% of GO patients). There were no significant differences in the changes from baseline to the peak values of alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphate, and total bilirubin within the follow-up period. The patients who did not receive ursodiol, however, had a higher incidence of grade 3 AST hepatotoxicity than their ursodiol counterparts (60% vs 20.8%, respectively; P = .015), and the median time to grade 3 AST hepatotoxicity was shorter in the group that did not receive ursodiol than in the group that received ursodiol (22.8 vs 37.8 days, respectively; P = .0016). Moreover, 4.2% of patients in the group that received ursodiol had SOS/VOD compared with none of the patients in the group that did not receive ursodiol. Of the 3 patients who had SOS/VOD, 2 (67%) received GO and had very severe classical disease, and 1 (33%) patient received InO and had mild, late-onset disease; all 3 patients were alive by the follow-up period.
CONCLUSION: Ursodiol prophylaxis treatment in adults with acute leukemia who were receiving GO/InO is not associated with lower incidences of hepatotoxicity or SOS/VOD. It is, however, associated with a significantly lower incidence of grade 3 AST hepatotoxicity, as well as a longer time to grade 3 AST hepatotoxicity compared with patients who did not receive ursodiol prophylaxis.
Previously presented at the American College of Clinical Pharmacy 2022 Annual Meeting and at the American Society of Health-System Pharmacists 2022 Midyear Clinical Meeting.
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