Real-world experience with inotuzumab ozogamicin in high-risk and R/R B-cell acute lymphoblastic leukemia.

Abstract

e18507 Background: Inotuzumab ozogamicin (InO) is an effective CD22-directed antibody–drug conjugate for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). However, real-world data describing dose-modified InO use in combination or as monotherapy, particularly in post-transplant settings and regions with a high prevalence of metabolic liver disease, is limited. Methods: We retrospectively analyzed consecutive patients with B-ALL treated with InO at our center from October 22,2022 to January 1, 2026. Data collected included demographics, disease biology, indication for InO use, combination with chemotherapy (mini-HCVD), InO dosing and cumulative exposure, response (CR/CRi and MRD), transplant outcomes, and toxicities including SOS/VOD and transplant-associated thrombotic microangiopathy (TA-TMA). Results: 15 patients with B-ALL were included (median age ~17 years; range 6–65); 53% had high-risk biology (TP53, IKZF+, or Ph+). InO was used as bridge to allo-HSCT (47%), post-allo relapse therapy (27%), post-allo maintenance (27%), sequentially with blinatumomab (20%), or as pre-phase stabilization (7%). Inotuzumab was administered in combination with mini-HCVD in 8 of 15 patients (53%), while the remainder received single-agent InO or other combinations based on disease burden and clinical context. All patients received 0.3 mg/m² per dose. The median number of doses was 4 (range 1–12), with a median cumulative dose of ~1.2 mg/m² (range 0.3–3.6 mg/m²), substantially lower than label-based cumulative exposure, reflecting combination therapy, frequent post-transplant use, and regional concern for baseline hepatic vulnerability including underlying fatty liver disease. Overall, CR/CRi was achieved in 80%, with MRD-negative CR in 60%, including patients with TP53-mutated and Ph+ disease. Among transplant-eligible patients, 70% were successfully bridged to allo-HSCT, and durable CR ≥12 months was observed in 40%. Severe SOS/VOD occurred in 1 patient (6.6%), in the post-allo relapse setting, and was fatal. TA-TMA was observed in 27%, clustering in post-allo settings. Conclusions: In this real-world cohort, dose-modified inotuzumab ozogamicin, frequently combined with mini-HCVD, produced high response and MRD-negativity across high-risk B-ALL. Toxicity appeared context-dependent even at lower doses, with rare but severe SOS/VOD and a notable endothelial toxicity signal in post-allo settings. These findings support cautious dosing and timing-based integration of inotuzumab ozogamicin, particularly in transplant-exposed populations and regions with prevalent metabolic liver disease. Parameter Result Patients (B-ALL) 15 Median age (range) ~17 years (6–65) High-risk biology 53% Inotuzumab + mini-HCVD 8 patients (53%) Median InO doses 4 (range 1–12) Median cumulative dose ~1.2 mg/m² CR/CRi 80% MRD-negative CR 60% SOS/VOD 6.6% TA-TMA 27%