e18512 Background: Inotuzumab ozogamicin (InO, CD22-directed) and blinatumomab (blina, CD19-directed) are increasingly used for pediatric relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), but the available evidence is dispersed across early-phase trials, multicenter cohorts and a single randomized comparison. We synthesized efficacy outcomes, including Minimal Residual Disease (MRD)-negative remission, Complete Remission (CR) and Overall Response Rate (ORR), as well as survival and we also evaluated safety outcomes such as Cytokine Release Syndrome (CRS), neurotoxicity and Sinusoidal Obstruction Syndrome or Veno Occlusive Disease (SOS/VOD), to inform treatment selection. Methods: We included phase I-III trials and multicenter cohorts published between 2015-2025 that reported at least 10 CD22-positive pediatric or Adolescent and Young Adult (AYA) patients with R/R B-ALL treated with InO or blina. The primary outcome was MRD-negative complete remission among morphological responders. Secondary outcomes included CR or ORR, grade ≥3 neurotoxicity, grade ≥3 CRS, SOS/VOD of any grade including post hematopoietic stem cell transplantation (HSCT) and Event Free Survival (EFS) or Overall Survival (OS). Single arm proportions were pooled using random effects models. Sensitivity analyses used the Freeman–Tukey method, REML and leave-one-out influence procedures. Estimates from the RCT by Locatelli in 2021 were extracted as hazard ratios and two arm risk ratios. RoB was assessed and evidence certainty was evaluated with GRADE. Results: Across 6 studies and 239 patients, MRD negativity pooled to 64% (95%CI 40–83%), with substantial heterogeneity (I 2 =76%). CR/ORR pooled to 64% (95%CI 40–83%) across 285 patients. Severe toxicities were infrequent: CRS ≥3 occurred in 1.9% (95% CI 0–13%) of 234 patients; neurotoxicity ≥3 in 4.5% (95%CI 3.1–6.5%) of 340 patients. SOS/VOD any-grade pooled to 7% (95% CI 1–33%), while post-HSCT SOS occurred in 29% (95%CI 6–59%) of 54 patients, predominantly following InO exposure. In the randomized trial (n=158), blina improved EFS (HR 0.45, 95%CI 0.36–0.55) and trended toward improved OS (HR 0.43, 95%CI 0.18–1.01). Two-arm analyses showed higher MRD negativity (RR 2.16, 95%CI 1.52–3.05) and CR/ORR (RR 1.69, 95%CI 1.27–2.25) with blina vs chemotherapy. Sensitivity analyses were concordant. Conclusions: In pediatric R/R CD22-positive B-ALL, CD22- and CD19-directed immunotherapies achieve high MRD-negative remission rates and substantial overall responses with low rates of severe CRS and neurotoxicity. InO is associated with a significant risk of post-HSCT SOS. These findings support the use of immunotherapy to achieve deep remission before transplant and highlight the need for careful VOD mitigation, optimized treatment sequencing and future randomized comparisons.
Parikh et al. (Thu,) studied this question.