Dose-dense mini–hyper-CVD + inotuzumab (CD22 ADC) + blinatumomab (CD19 BiTE) drives ~95% NGS-MRD negativity in R/R B-ALL, with better 2-year survival when consolidated with CAR-T/SCT

Dose-dense mini–hyper-CVD chemotherapy combined with inotuzumab ozogamicin (anti-CD22 calicheamicin ADC) and blinatumomab (CD19×CD3 bispecific T-cell engager) was evaluated in a Phase 2 study in adults with relapsed/refractory Ph+ or Ph− B-ALL (n=27; 89% in first salvage; 33% previously exposed to blina; 24% TP53-mutated; 30% Ph-like among Ph−). All patients achieved CR/CRi (81% CR), with MRD negativity rates of 96% by flow and 95% by NGS; after cycle 1, 80% were flow-MRD negative but only 44% were NGS-MRD negative (suggesting deeper clearance lagged behind conventional MRD). At median follow-up 32 months, 2-year OS/EFS were 68%/79% overall; outcomes appeared best with post-remission consolidation (2-year OS 89% with CAR-T; 100% with alloSCT; 55% with no consolidation), and CAR-T deepened responses further (10/11 [91%] achieved/maintained NGS-MRD negativity post–CAR-T). These remission depth and 2-year survival rates look meaningfully above historical single-agent immunotherapy benchmarks in R/R adult B-ALL (e.g., INO-VATE inotuzumab median OS ~7.7 months vs ~6.2 months with SOC chemo), though this abstract does not report Grade 3+ AEs (critical given InO-associated VOD/SOS risk and blina CRS/ICANS).