Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE

Cancer. 2018 Apr 15;124(8):1722-1732. doi: 10.1002/cncr.31249. Epub 2018 Jan 30.

Abstract

Background: Inotuzumab ozogamicin (InO) has demonstrated efficacy and tolerability in patients aged 18 to 78 years with relapsed/refractory acute lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared the efficacy and safety of InO in younger and older patients.

Methods: Intent-to-treat analyses of morphologic responses and overall survival (OS) included 326 randomized patients, and safety assessments included 307 patients receiving 1 or more doses of the study treatment. Of the 326 patients, 164 received InO at a starting dose of 1.8 mg/m2 /cycle (0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 of a 21- to 28-day cycle [≤6 cycles]); 60 patients were aged ≥55 years, and 104 were aged <55 years.

Results: For older and younger patients, the median duration of InO therapy and the types and frequencies of adverse events of any grade were generally similar. Although the remission rates, median duration of remission (DOR), and progression-free survival were similar with InO for those aged <55 years and those aged ≥55 years, OS was longer for younger patients (median, 8.6 vs 5.6 months; hazard ratio, 0.610). Among patients proceeding to hematopoietic stem cell transplantation after InO treatment (28% of older patients and 58% of younger patients), the incidence of veno-occlusive disease was greater in older patients (41% vs 17%). The study database was not locked at the time of this analysis.

Conclusions: InO was tolerable in older patients with relapsed/refractory ALL. Although OS was longer for younger patients versus older patients, InO demonstrated high response rates with similar DOR in the 2 age groups. Cancer 2018;124:1722-32. © 2018 American Cancer Society.

Trial registration: ClinicalTrials.gov NCT01564784.

Keywords: acute lymphoblastic leukemia (ALL); elderly; inotuzumab ozogamicin; safety; veno-occlusive disease (VOD).

Publication types

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

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Female
  • Hematopoietic Stem Cell Transplantation / statistics & numerical data
  • Hepatic Veno-Occlusive Disease / chemically induced
  • Hepatic Veno-Occlusive Disease / epidemiology*
  • Humans
  • Incidence
  • Inotuzumab Ozogamicin
  • Intention to Treat Analysis
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Progression-Free Survival
  • Young Adult

Substances

  • Antibodies, Monoclonal, Humanized
  • Inotuzumab Ozogamicin

Associated data

  • ClinicalTrials.gov/NCT01564784