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

Abstract

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. 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. 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. 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.