Patient-Reported Outcomes from a Global Phase 3 Randomized Controlled Trial of Inotuzumab Ozogamicin Versus Standard of Care Chemotherapy for Relapsed/Refractory Acute Lymphoblastic Leukemia

• Published in: Blood 2016-12, Vol.128 (22), p.1599-1599
• Main Authors: Kantarjian, Hagop M., Su, Yun, Jabbour, Elias J., Bhattacharyya, Helen, Yan, Eric, Shapiro, Mark, Cappelleri, Joseph C., Marks, David I.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V128.22.1599.1599

Background: Inotuzumab Ozogamicin (InO), an anti-CD22 antibody-calicheamicin conjugate, has demonstrated superior clinical activity versus standard of care (SOC; intensive chemotherapy) for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) in the phase 3 INO-VATE trial (Kantarjian. N Engl J Med. June 12, 2016 [E-pub]). A previous intent-to-treat (ITT) analysis of patient-reported outcomes (PROs) in 279 randomized patients demonstrated that InO is associated with generally better quality of life (QoL), functioning, and symptoms versus SOC (Kantarjian. J Clin Oncol 34, 2016 [abstract 7027]; data cutoff date, October 2, 2014). Herein, updated PROs results from 326 randomized patients are presented (data cutoff date, March 8, 2016; median follow-up, 6.6 [range, 0.03-39.75] months; long-term safety follow-up is ongoing). Methods: Patients were randomized to InO (max 1.8 mg/m2/cycle [≤6 cycles]) or SOC (fludarabine/cytarabine [ara-C]/granulocyte colony-stimulating factor, ara-C + mitoxantrone, or high-dose ara-C [≤4 cycles]) and completed the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EuroQoL 5 Dimensions questionnaire (EQ-5D) Index and EQ visual analogue scale (EQ-VAS) at baseline, day 1 of each cycle, and end of treatment. Treatment differences in PRO measures over time were assessed in the ITT populationusing longitudinal mixed-effects models with random intercepts and slopes with treatment, time, treatment-by-time interaction, and baseline scores as covariates. Analyses were supportive and no multiplicity adjustments were made. Results: EORTC QLQ-C30 completion rates in patients receiving InO and SOC who completed ≥1 question were 85% and 65%, respectively; EQ-5D completion rates were similar. Baseline PRO scores were in general comparable for InO (n=164) and SOC (n=162) arms (eg, mean [SE] EORTC QLQ-C30 Global Health Status/QoL, 56.51 [2.06] vs 55.24 [2.18]; Physical, 73.69 [1.78] vs 73.48 [2.08], Role, 57.17 [2.67] vs 62.36 [2.97], Social functioning, 62.03 [2.52] vs 55.16 [3.17]; Appetite loss, 20.97 [2.31] vs 21.84 [2.62]; Dyspnea, 20.53 [2.34] vs 22.13 [2.55]; Fatigue, 40.84 [2.08] vs 40.23 [2.46]; EQ-5D Index, 0.77 [0.01] vs 0.76 [0.02]; EQ-VAS, 59.79 [2.12] vs 62.27 [2.03]). Compared with SOC, patients receiving InO reported numerically better QoL, functioning, and symptom scores (except for Constipation and Emotional functioning). After adjusting for baseline scores