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

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2018-12, Vol.18 (12), p.803-813.e7
• Main Authors: Barrientos, Jacqueline C., O’Brien, Susan, Brown, Jennifer R., Kay, Neil E., Reddy, Nishitha M., Coutre, Steven, Tam, Constantine, Mulligan, Stephen, Jaeger, Ulrich, Devereux, Stephen, Pocock, Christopher, Robak, Tadeusz, Schuster, Stephen J., Schuh, Anna, Gill, Devinder, Bloor, Adrian, Dearden, Claire, Moreno, Carol, Cull, Gavin, Hamblin, Mike, Jones, Jeffrey A., Eckert, Karl, Solman, Isabelle G., Suzuki, Samuel, Hsu, Emily, James, Danelle F., Byrd, John C., Hillmen, Peter
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Bruton's tyrosine kinase; Disease-related symptoms; Erythrocyte Indices; Fatigue; Female; Follow-Up Studies; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - blood; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - epidemiology; Leukocyte Count; Male; Patient Acceptance of Health Care; Patient Reported Outcome Measures; Quality of Life; Recurrence; Relapsed/refractory CLL/SLL; Symptom Assessment; Treatment Outcome
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2018.08.007

In the phase III study RESONATE, ibrutinib reduced the risk of progression and improved overall survival versus ofatumumab in previously treated patients with CLL/SLL. In this novel analysis of patient well-being including patient-reported outcomes, ibrutinib reduced disease burden while preserving parameters of hematologic and immunologic function in RESONATE. These results suggest that ibrutinib can improve quality of life while prolonging survival. Ibrutinib compared with ofatumumab significantly improves progression-free and overall survival in patients with previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 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. 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. 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.