Utility of ursodiol prophylaxis against sinusoidal obstruction syndrome (SOS)/ veno-occlusive disease (VOD) in acute leukemia patients receiving gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO).

Purpose: Sinusoidal obstructive syndrome (SOS)/veno-occlusive disease (VOD) is a serious complication in hematopoietic stem-cell transplant (HSCT) patients. Gemtuzumab-ozogamicin (GO) and InO are known to cause SOS/VOD in leukemic and transplant populations. Due to limited data on ursodiol prophylaxis in non-HSCT patients, we aimed to assess hepatotoxicity, SOS/VOD incidences, time to hepatotoxicity, and confirmed SOS/VOD in adults receiving GO or InO ± ursodiol.

Methods: A multicenter, retrospective chart review of adult acute leukemia patients who received ≥1 dose of GO or InO at DFCI/some of the Harvard Cancer Centers during 4-year period (9/1/2017-9/1/2021). Acute promyelocytic leukemia patients and post-GO or InO HSCT-recipients (100-day follow-up period) were excluded. Descriptive summaries are provided, direct comparisons were made using Student T-test (continuous variables) and Fisher's exact test (categorical variables).

Results: In our population (N = 82), 87.8% received ursodiol and 12.2% did not. There were no significant differences in baseline to peak hepatic labs. The No-Ursodiol Group had higher incidence of Grade 3 aspartate aminotransferase (AST) transaminitis vs. the Ursodiol Group (60% vs. 20.8%; p = 0.015), and a trend towards shorter mean time to Grade 3 AST transaminitis (18.5 vs. 23.8 days; p = 0.30). Moreover, 4.2% of Ursodiol Group developed SOS/VOD vs. 0% in the No-Ursodiol Group (NS). Three patients developed SOS/VOD: 2 received GO, 1 received InO, and 2 were alive by the end of the follow-up period.

Conclusion: In our cohort, ursodiol prophylaxis in adults receiving GO/InO is not associated with lower incidences of hepatotoxicity, SOS/VOD, or time to Grade 3 AST transaminitis, but is associated with decreased incidence of AST elevations.