Ursodiol falls short of preventing SOS/VOD in GO/InO-treated leukaemia patients

In acute leukaemia patients being treated with gemtuzumab-ozogamicin (GO) or inotuzumab-ozogamicin (InO), use of ursodiol prophylaxis does not appear to reduce the incidences of hepatoxicity, sinusoidal obstruction syndrome (SOS) or veno-occlusive disease (VOD), or time to grade 3 aspartate aminotransferase (AST) transaminitis, a study has shown.

Eighty-two adult patients with acute leukaemia who received at least a single dose of GO or InO during a 4-year period (2017‒2021) were included in this multicentre, retrospective chart review. Those with acute promyelocytic leukaemia and post-GO or InO haematopoietic stem-cell transplant recipients (100-day follow-up period) were excluded from the study.

The investigators provided descriptive summaries and made direct comparisons using Student T-test (continuous variables) and Fisher’s exact test (categorical variables).

Of the 82 patients, 87.8 received ursodiol and 12.2 percent did not. No significant differences in baseline to peak hepatic labs were observed.

Compared with the no-ursodiol group, the ursodiol group had a lower incidence of grade 3 AST transaminitis (60 percent vs 20.8 percent; p=0.015) and showed a trend towards a longer mean time to grade 3 transaminitis (18.5 vs 23.8 days; p=0.30).

In addition, 4.2 percent of patients who received ursodiol developed SOS/VOD relative to none in those who did not receive ursodiol. Specifically, three patients developed SOS/VOD: two received GO, one received InO, and two were alive by the end of the follow-up period.

“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,” the investigators said.

SOS/VOD is a serious complication in HSCT recipients, while GO and InO are believed to induce SOS/VOD in leukaemic and transplant patients.