Improvement in Parameters of Hematologic and Immunologic Function and Patient Well-being in the Phase III RESONATE Study of Ibrutinib Versus Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Abstract

BACKGROUND:

Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

PATIENTS AND METHODS:

Measures of well-being were assessed in RESONATE, where previously treated patients with CLL/SLL were randomized to receive ibrutinib 420 mg/day (n = 195) or ofatumumab (n = 196) for up to 24 weeks. Endpoints included hematologic function, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), disease-related symptoms, European Organization for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 (EORTC QLQ-C30), and medical resource utilization.

RESULTS:

With up to 24 months' follow-up (median, 16.4 months), 79% of cytopenic patients showed sustained hematologic improvement (82% with improved platelet count, 69% with improved hemoglobin) on ibrutinib versus 43% on ofatumumab (P < .0001). Higher rates of clinically meaningful improvement were demonstrated with ibrutinib versus ofatumumab for FACIT-F and EORTC global health. Greater improvement was observed in disease-related weight loss, fatigue, night sweats, and abdominal discomfort with ibrutinib versus ofatumumab. Hospitalizations in the first 30 days occurred less frequently with ibrutinib than ofatumumab (0.087 vs. 0.184 events/patient; P = .0198). New-onset diarrhea was infrequent with ibrutinib after the first 6 months (47% at ≤6 months vs. 5% at 12-18 months). With ibrutinib, grade ≥ 3 hypertension occurred in 6%, grade ≥ 3 atrial fibrillation in 4%, major hemorrhage in 2%, and tumor lysis syndrome in 1% of patients.

CONCLUSION:

Ibrutinib led to significant improvements in hematologic function and disease symptomatology versus ofatumumab, and can restore quality of life while prolonging survival in relapsed/refractory CLL/SLL.

• Authors: Jacqueline C Barrientos, Susan O'Brien, Jennifer R Brown, Neil E Kay, Nishitha M Reddy, Steven Coutre, Constantine Tam, Stephen Mulligan, Ulrich Jaeger, Stephen Devereux, Christopher Pocock, Tadeusz Robak, Stephen J Schuster, Anna Schuh, Devinder Gill, Adrian Bloor, Claire Dearden, Carol Moreno, Gavin Cull, Mike Hamblin, Jeffrey A Jones, Karl Eckert, Isabelle G Solman, Samuel Suzuki, Emily Hsu, Danelle F James, John C Byrd, Peter Hillmen
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 18 Issue 12 Pg. 803-813.e7 (12 2018) ISSN: 2152-2669 [Electronic] United States
• PMID: 30249389 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Biomarkers
• Erythrocyte Indices
• Female
• Follow-Up Studies
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (blood, diagnosis, drug therapy, epidemiology)
• Leukocyte Count
• Male
• Patient Acceptance of Health Care
• Patient Reported Outcome Measures
• Quality of Life
• Recurrence
• Symptom Assessment
• Treatment Outcome