Patient-reported outcomes from a phase 3 randomized controlled trial of inotuzumab ozogamicin versus standard therapy for relapsed/refractory acute lymphoblastic leukemia

Cancer. 2018 May 15;124(10):2151-2160. doi: 10.1002/cncr.31317. Epub 2018 Mar 6.

Abstract

Background: Inotuzumab ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, demonstrated superior clinical activity versus standard-of-care (SOC) chemotherapies for relapsed/refractory B-cell acute lymphoblastic leukemia in the phase 3 randomized controlled INO-VATE trial. The authors assessed patient-reported outcomes (PROs) from that study.

Methods: Patients were randomized to receive either InO (1.8 mg/m2 per cycle for ≤6 cycles) or SOC (fludarabine/cytarabine [ara-C]/granulocyte colony-stimulating factor, or ara-C plus mitoxantrone, or high-dose ara-C for ≤4 cycles) and completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the EuroQoL 5 Dimensions Questionnaires at baseline, on day 1 of each cycle, and at the end of treatment. Treatment differences in PROs were assessed using longitudinal mixed-effects models with random intercepts and slopes.

Results: Questionnaire completion rates in the InO (n = 164) and SOC (n = 162) arms were 85% and 65%, respectively. Baseline scores were similar between arms. Patients who received InO reported better quality of life (QoL), functioning, and symptom scores (except for constipation and emotional functioning). Least-squares mean (95% confidence interval [CI]) differences in physical, role, and social functioning and in appetite loss were significant (6.9 [95% CI, 1.4-12.3], 11.4 [95% CI, 3.2-19.5], 8.4 [95% CI, 0.7-16.1], and -8.7 [95% CI, -16.0 to -1.4], respectively; all P < .05) and had exceeded the minimally important difference of 5. Mean treatment differences in favor of InO on the EuroQoL visual analog scale and the global health status/QoL, dyspnea, and fatigue scales reached or approached the minimally important difference of 5, although without statistical significance. No dimensions were significantly worse with InO versus SOC.

Conclusions: The current PRO data support the favorable benefit/risk ratio of InO for the treatment of relapsed/refractory acute lymphoblastic leukemia, with superior clinical efficacy and better QoL. Cancer 2018;124:2151-60. © 2018 American Cancer Society.

Keywords: acute lymphoblastic leukemia; clinical study; inotuzumab ozogamicin; patient-reported outcomes; quality of life.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Resistance, Neoplasm
  • Dyspnea / chemically induced
  • Dyspnea / epidemiology
  • Fatigue / chemically induced
  • Fatigue / epidemiology
  • Female
  • Follow-Up Studies
  • Health Status
  • Humans
  • Inotuzumab Ozogamicin
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Patient Reported Outcome Measures*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / microbiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Quality of Life
  • Sialic Acid Binding Ig-like Lectin 2 / antagonists & inhibitors
  • Sialic Acid Binding Ig-like Lectin 2 / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • CD22 protein, human
  • Sialic Acid Binding Ig-like Lectin 2
  • Inotuzumab Ozogamicin