Low incidence of hepatic veno-occlusive disease (VOD) in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with inotuzumab ozogamicin (INO) followed by allogeneic stem cell transplantation (allo-SCT).

Abstract

e19024 Background: Hepatic VOD is an uncommon, but often fatal complication of allo-SCT. The risk is increased after INO, an anti-CD22 antibody conjugated to calicheamicin with high remission rates in relapsed CD22-positive B-ALL. Previous reports have described VOD rates as high as 19% in INO-treated patients who then received allo-SCT. We report our safety experience using INO followed by allo-SCT. Methods: We identified patients >18 yrs with B-ALL treated with allo-SCT and INO in the University of Chicago IRB-approved SCT database. We reviewed the EMR for patient details, toxicities (CTCAE v5.0), and outcomes. Hepatic VOD was defined according to EBMT criteria. Overall survival (OS) was from time of allo-SCT to death or last follow-up. Results: Between 2010-2021, 72 adult patients with B-ALL received allo-SCT, and 17 also received INO as salvage therapy (Table). Median follow-up was 19 months (1-110). All received ursodiol prophylaxis and 15/17 received an azole for antifungal prophylaxis. They had median 2 cycles (1-3) of INO with median of 1.9 months (1-14) from the last dose of INO to allo-SCT. For cycle 1, 13/17 (77%) received 0.8 mg/m2 on D1 and 0.5 mg/m2 on D8 and D15. Of these, 11 had a subsequent cycle (5 with same dosing and 7 had 0.5 mg/m2 on D1, D8, and D15). 1 patient had 0.5 mg/m2 on D1, D8, and D15 for 2 cycles. 3 patients received 0.8 mg/m2 on D1 and 0.4 mg/m2 on D8 and D15 for 2 cycles. After INO, 10 patients achieved CR and 3 had CRi for ORR of 13/17 (76%). The 4 patients with persistent disease despite INO went into remission with a different salvage therapy prior to allo-SCT. Conditioning regimens are listed in Table 1. No patients developed VOD after allo-SCT. Within 2 yrs of allo-SCT, 3/17 (18%) relapsed and 7/17 (41%) died. The median OS was 21.2 months [18 - NR]. Conclusions: Limiting the number of INO cycles (median 2) prior to allo-SCT, delaying allo-SCT for 2 months after INO exposure, and avoiding dual alkylating agent conditioning may have contributed to the absence of VOD in our patients. Larger data sets will be useful to validate these important safety observations.[Table: see text]