Sinusoidal obstruction syndrome and other outcomes in pediatric patients with acute lymphoblastic leukemia who received inotuzumab ozogamicin before hematopoietic cell transplantation.

e22000 Background: Inotuzumab ozogamicin (InO) is FDA approved for adult and pediatric (≥1 y) patients (pts) with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). However, InO has been associated with increased risk of sinusoidal obstruction syndrome (SOS), particularly following hematopoietic cell transplantation (HCT). Previously reported post-HCT SOS rates are ~20% in adults and ~20–50% in pediatric pts who received InO before HCT. Methods: This observational, post-authorization safety study used data from the CIBMTR to assess post-HCT outcomes in pts with B-cell precursor ALL who received InO prior to HCT in the US. We report outcomes in pediatric pts ( < 18 y) who received InO prior to first HCT between 18 Aug 2017 and 17 Aug 2022. Results: In all, 52 pts were included (median age 9 y; 54% male; 83% with R/R ALL). Prior to HCT, 17% were in first complete remission (CR1), 40% in CR2, and 42% in CR≥3; 52%, 42%, and 6% received 1, 2, and ≥3 InO cycles, respectively; 46% received InO as monotherapy and 35% in combination with other agents (data unavailable in 19%). After InO, 39/52 (75%) achieved CR and 9/52 (17%) achieved CR with incomplete hematologic recovery; 38/47 (81%) evaluable pts were reported as minimal residual disease negative. Median (range) time from last InO dose to HCT was 1.4 (0.6–12.5) mo. Post-HCT outcomes are shown in the table. Post-HCT relapse of ALL occurred in 21 pts, of whom 7 (33%) died within 18 mo. Of 31 pts without post-HCT relapse, 6 died in remission due to SOS (n = 2), graft-versus-host disease (GVHD), organ failure, infection, or thrombotic microangiopathy (n = 1 each). In all, 16 pts developed SOS (8 mild; 8 severe). Of these, 7 received defibrotide treatment and 7 died within 18 mo (2 with SOS as cause of death). Prophylactic defibrotide was given to 23/52 pts (7/16 with SOS). Median (range) time from HCT to SOS was 10 (6–25) d. Other adverse events occurring in ≥30% of pts 100 d post HCT were viral infection (38%) and acute grade II–IV GVHD (33%). Conclusions: The rate of SOS in this real-world cohort of pediatric pts with ALL who received InO before HCT was similar to prior pediatric clinical studies. Given the high SOS rate and mortality in pediatric pts, careful consideration and pt selection should be exercised when using InO prior to HCT. Further investigation is needed to identify SOS risk factors and strategies for mitigating this risk in pediatric pts. Post-HCT outcomes. Pediatric ptsn=52 Median (range) follow-up from HCT, mo 15.2 (3.3–50.7) 12-mo overall survival % (95% CI) 71 (56–83) 6-mo transplant-related mortality, % (95% CI) 8 (2–17) 6-mo non–transplant-related mortality % (95% CI) 8 (3–17) 6-mo relapse, % (95% CI) 24 (13–37) Continued CR, n (%) 51 (98) Pts with SOS within 100 d, n 16 100-d SOS, % (95% CI) 31 (19–44) Post-SOS mortality among all pts, n (%) 7 (13)