Time to First Subsequent Salvage Therapy in Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Treated With Inotuzumab Ozogamicin in the Phase III INO-VATE Trial

Clin Lymphoma Myeloma Leuk. 2022 Sep;22(9):e836-e843. doi: 10.1016/j.clml.2022.04.022. Epub 2022 Apr 27.


Background: In relapsed/refractory acute lymphoblastic leukemia (R/R ALL), successive salvage therapies may worsen outcomes and decrease quality of life. This post hoc analysis of the phase III INO-VATE trial investigates subsequent salvage therapies and compared the time from randomization to first subsequent salvage therapy (TST) in the inotuzumab ozogamicin (InO) and standard-of-care chemotherapy (SoC) arms.

Patients and methods: Adults (aged ≥18 years) with CD22+ R/R ALL were randomized to InO (n = 164) or SoC (n = 162) treatment. We determined TST and proportion of patients receiving subsequent salvage therapies by treatment arm and for subgroups based on transplantation status and baseline characteristics.

Results: In the InO versus SoC arm, a smaller proportion of patients received subsequent salvage therapy (34.1% [n = 56] vs. 56.8% [n = 92]), and TST was longer (median 19 vs. 4 months, hazard ratio 0.339, P < .0001). Similar benefits were seen with InO versus SoC irrespective of transplantation status, age, salvage phase, first remission duration, Philadelphia chromosome status, or CD22 expression. Following receipt of subsequent salvage therapy, median overall survival was 4 months, irrespective of treatment arm.

Conclusion: Patients in the InO versus SoC arm were less likely to receive subsequent salvage therapy, and showed a clinically meaningful extension of TST irrespective of subgroup. This suggests InO treatment leads to improved outcomes by increasing the likelihood that subsequent salvage therapies and their associated adverse impacts can be delayed or avoided.

Plain language summary: Available in Supplementary Materials.

Clinical trial registration: NCT01564784.

Keywords: ALL; Inotuzumab ozogamicin; TST; TTNT; Time to next treatment.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Humans
  • Inotuzumab Ozogamicin / pharmacology
  • Inotuzumab Ozogamicin / therapeutic use
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Quality of Life
  • Salvage Therapy*
  • Standard of Care


  • Inotuzumab Ozogamicin

Associated data

  • ClinicalTrials.gov/NCT01564784