Background: In INO-VATE, patients (pts) treated with InO vs standard chemotherapy (SC) had significantly greater remission rates and longer overall survival (OS), with 23% reduced risk of death (Kantarjian et al, NEJM 2016). Here we report detailed safety outcomes from long-term follow-up. Methods: Study methods were previously published. Adults with CD22+ ALL in 1st or 2nd salvage were randomized 1:1 to InO (n = 164) or SC (n = 162). Data up to Jan 4, 2017 are reported. Results: Adverse event (AE) and serious AE rates were similar between arms even though more cycles of InO than SC were administered (Table). Grade (Gr) 3-4 AE rates were higher with SC, while more Gr 5 AEs occurred with InO vs SC (6% vs 2%); 5 cases (3%) were veno-occlusive disease (VOD). More pts taking InO discontinued due to AEs, most often from infections (10 [6%]) including pneumonia and sepsis, hepatobiliary disorders (7 [4%]), or blood/lymphatic disorders (BLD) including cytopenias (5 [3%]). For SC, discontinuations were most often from infections (6 [4%]) or BLD (3 [2%]). More hepatic AEs (any Gr) occurred with InO: 83 (51%) vs 52 (36%), including VOD (23 [14%] vs 3 [2%]). A lower percentage of death was seen with InO: 131 (80%) vs 126 (88%) for SC. Fewer InO pts died from ALL: 80 (49%) vs 100 (70%) for SC. Clinical trial information: NCT01564784Conclusions: Safety data from the final report of INO-VATE are consistent with previous reports of data that also include greater efficacy (longer survival) seen with InO vs SC. Temporary discontinuation and dose reduction of InO were used to manage serious or severe AEs. Data suggest vigilant monitoring, treatment, and/or prevention for the most common events such as VOD and infections are needed to optimize outcomes.