{"entity":{"id":"paper-ino-vate-inotuzumab-all-nejm-2016","kind":"paper","name":"INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa1509277"},{"label":"ClinicalTrials.gov NCT01564784","url":"https://clinicaltrials.gov/study/NCT01564784"}],"tags":[],"related":["inotuzumab-then-transplant-caution"],"cancers":["all-leukemia"],"sections":[],"technologies":["adc","allogeneic-hsct"],"targets":["cd22"],"drugs":["inotuzumab-ozogamicin","blinatumomab"],"companies":["pfizer"],"institutions":["md-anderson"],"pathways":[],"terms":["mrd","os"],"trials":[],"people":["hagop-kantarjian"],"bottlenecks":["b-toxicity-qol"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2016,"doi":"10.1056/NEJMoa1509277","authors":"Kantarjian HM, DeAngelo DJ, Stelljes M, et al.","paperType":"rct","findings":["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."],"whatItMeans":"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.","caveats":["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."],"changedPractice":true,"participants":326},"route":"/key-papers/paper-ino-vate-inotuzumab-all-nejm-2016/","neighbours":{"pairing":[{"id":"inotuzumab-then-transplant-caution","kind":"pairing","name":"Caution: inotuzumab before transplant (veno-occlusive disease)","route":"/pairings/inotuzumab-then-transplant-caution/"}],"cancer":[{"id":"all-leukemia","kind":"cancer","name":"Acute lymphoblastic leukaemia","route":"/cancers/all-leukemia/"}],"technology":[{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"adc","kind":"technology","name":"Antibody-drug conjugate (ADC)","route":"/technologies/adc/"}],"target":[{"id":"cd22","kind":"target","name":"CD22","route":"/targets/cd22/"}],"drug":[{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"inotuzumab-ozogamicin","kind":"drug","name":"Inotuzumab ozogamicin","route":"/drugs/inotuzumab-ozogamicin/"}],"company":[{"id":"pfizer","kind":"company","name":"Pfizer (incl. Seagen)","route":"/companies/pfizer/"}],"institution":[{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"os","kind":"term","name":"Overall survival (OS)","route":"/terms/os/"}],"person":[{"id":"elias-jabbour","kind":"person","name":"Elias Jabbour","route":"/people/elias-jabbour/"},{"id":"hagop-kantarjian","kind":"person","name":"Hagop M. Kantarjian","route":"/people/hagop-kantarjian/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}