INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL
A CD22 antibody-drug conjugate produced complete remission in 81% of adults with relapsed ALL compared with 29% on chemotherapy, at the cost of liver toxicity in about one in ten.
INO-VATE randomised 326 adults with relapsed or refractory CD22-positive B-cell ALL to inotuzumab ozogamicin or standard intensive salvage chemotherapy. The two primary endpoints were complete remission (analysed in the first 218 patients) and overall survival. Complete remission was 80.7% versus 29.4%, with MRD-negativity among responders 78.4% versus 28.1%, and median PFS 5.0 versus 1.8 months. Median OS was 7.7 versus 6.7 months (hazard ratio 0.77), which did not meet the prespecified boundary, although two-year survival was 23% versus 10%. Hepatic veno-occlusive disease occurred in 11% of inotuzumab patients, especially after subsequent transplant with dual-alkylator conditioning.
- 326 adults with relapsed/refractory B-ALL; inotuzumab ozogamicin vs salvage chemotherapy.
- Complete remission 80.7% vs 29.4%; MRD-negativity among responders 78.4% vs 28.1%.
- Median PFS 5.0 vs 1.8 months; more patients bridged to transplant (41% vs 11%).
- Median OS 7.7 vs 6.7 months (HR 0.77); 2-year OS 23% vs 10%.
- Veno-occlusive disease 11% vs 1%, highest after transplant with dual-alkylator conditioning.
INO-VATE made inotuzumab a standard salvage therapy for adult ALL and a common route to transplant, and, with the TOWER trial of blinatumomab, moved adult ALL from chemotherapy-only salvage to immunotherapy. Both drugs have since been pulled into front-line regimens. The liver toxicity signal shaped how transplant conditioning is chosen after inotuzumab.
- OS benefit was modest and did not meet the trial's statistical threshold at the primary analysis.
- Veno-occlusive disease is a serious, sometimes fatal, toxicity that constrains dosing before transplant.
- Open-label with heterogeneous chemotherapy comparators.
- Requires CD22 expression; antigen loss is a resistance mechanism.