P376: veno-occlusive disease risk and other outcomes in patients with b-cell precursor acute lymphoblastic leukemia receiving inotuzumab ozogamicin and proceeding to hematopoietic stem cell transplantation

Background: Inotuzumab ozogamicin (InO) is a CD22-directed antibody–drug conjugate indicated for R/R B-cell precursor ALL. InO has been associated with hepatotoxicity and hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), particularly after HSCT. Aims: Post-HSCT outcomes in patients (pts) who received InO before HSCT. Methods: This observational, post-authorization safety study included pts in the US with B-cell precursor ALL who received InO and proceeded to first allogeneic HSCT, with data reported to CIBMTR. We report outcomes in pts (≥18 y) with ALL, and the subset of pts with R/R ALL. Post-HSCT outcomes included overall survival (OS), non-relapse mortality (NRM), relapse, and AEs. Multivariate analyses examined prognostic factors for NRM and VOD/SOS. This final analysis is based on 5-y data (18 Aug 2017–17 Aug 2022). Results: There were 261 pts with ALL (median age 39 y, 58% male): 36% in first complete remission (CR1), 46% in CR2, 11% in CR≥3, 4% in first relapse, 1% in ≥third relapse, and 2% with primary induction failure. Prior to HSCT, respectively, 32%, 47%, 14%, 5%, and <1% received 1, 2, 3, 4, and 5 InO cycles; 120 and 112 pts received InO as monotherapy or in combination with systemic therapy (data unavailable in 29 pts). CR/CRi and MRD negativity was achieved in 80% and 64% of pts, respectively, after InO. Median (range) time from last InO dose to HSCT was 2.4 (0.6–26.2) mo. Post-HSCT outcomes are shown in Table 1. Post-HSCT OS at 18 mo was 54% in pts with ALL and 50% in pts with R/R ALL. Correspondingly, NRM within 18 mo was observed in 22% and 25% of pts; most common causes were VOD/SOS (26%, 24%) and graft-versus-host disease (GVHD; 22%, 19%). AEs occurring in ≥30% of pts with ALL and R/R ALL, respectively, within 100 d post-HSCT were bacterial infection (51%, 56%), viral infection (44%, 44%), and acute GVHD (grades II–IV; 43%, 41%). Of 35 pts with ALL who developed VOD/SOS, 15 cases were mild and 20 were severe, and 22 pts died within 18 mo post-HSCT; 8/35 pts received prophylactic defibrotide (22/244 of all pts). Transplant sources for the 15 mild and 20 severe cases of VOD/SOS: 10 and 12 were from peripheral blood stem cells, 4 and 8 from bone marrow, and 1 and 0 from umbilical cord blood, respectively. VOD/SOS incidence within 100 d post-HSCT was, respectively: 20%, 17%, 10%, and 16% in pts with cumulative InO doses of <1.8, 1.8–2.7, 2.8–3.2, and ≥3.3 mg/m2; and 15%, 25%, 17%, and 14% in pts with time from last InO dose to HSCT of <1, 1.1–1.6, 1.7–3, and ≥3 mo. 204 pts with ALL were included in multivariate analyses. Karnofsky score <90 or unknown (vs 90-100: hazard ratio [HR], 3.00, 7.55; P=0.0010, <0.0001) and dual alkylators (compared by MAC/no dual alkylators and RIC/non-MAC: HR, 0.15, 0.26; P=<0.0001, 0.0027) were negative prognostic factors for NRM at 18 mo. Dual alkylators were the only negative prognostic factor for VOD/SOS at 100 d (compared by MAC/no dual alkylators and RIC/non-MAC: odds ratio, 0.26, 0.15; P=0.0275, 0.0032). Summary/Conclusion: In this real-world population of adults with ALL who received InO before HSCT, including heavily pretreated pts, 18-mo OS was 54% and 18-mo NRM was 22%. Common AEs post-HSCT were bacterial infection, viral infection, and acute GVHD. VOD incidence was consistent with previous reports and dual alkylators should be avoided, when possible, in this subset of pts. Pts receiving these regimens should be considered for clinical trials testing novel prophylactic treatments for post-HSCT endothelial dysfunction syndromes, such as VOD.Keywords: Acute lymphoblastic leukemia, B cell acute lymphoblastic leukemia