# INO-VATE: inotuzumab ozogamicin, a CD22 antibody-drug conjugate, versus chemotherapy for relapsed adult B-cell ALL

Source: https://onco.cc/key-papers/paper-ino-vate-inotuzumab-all-nejm-2016/  
OnCo record `paper-ino-vate-inotuzumab-all-nejm-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2016
- DOI: 10.1056/NEJMoa1509277
- Authors: Kantarjian HM, DeAngelo DJ, Stelljes M, et al.
- 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.
- What it means: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa1509277
- ClinicalTrials.gov NCT01564784: https://clinicaltrials.gov/study/NCT01564784

## Connected records

- pairings: [Caution: inotuzumab before transplant (veno-occlusive disease)](https://onco.cc/pairings/inotuzumab-then-transplant-caution/)
- cancers: [Acute lymphoblastic leukaemia](https://onco.cc/cancers/all-leukemia/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/)
- targets: [CD22](https://onco.cc/targets/cd22/)
- drugs: [Blinatumomab](https://onco.cc/drugs/blinatumomab/), [Inotuzumab ozogamicin](https://onco.cc/drugs/inotuzumab-ozogamicin/)
- companies: [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/)
- institutions: [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Overall survival (OS)](https://onco.cc/terms/os/)
- people: [Elias Jabbour](https://onco.cc/people/elias-jabbour/), [Hagop M. Kantarjian](https://onco.cc/people/hagop-kantarjian/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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