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

被引：32

作者：

Barrientos, Jacqueline C. ^{[1
]}

O'Brien, Susan ^{[2
]}

Brown, Jennifer R. ^{[3
]}

Kay, Neil E. ^{[4
]}

Reddy, Nishitha M. ^{[5
]}

Coutre, Steven ^{[6
]}

Tam, Constantine ^{[7
,8
]}

Mulligan, Stephen ^{[9
]}

Jaeger, Ulrich ^{[10
]}

Devereux, Stephen ^{[11
]}

Pocock, Christopher ^{[12
]}

Robak, Tadeusz ^{[13
]}

Schuster, Stephen J. ^{[14
]}

Schuh, Anna ^{[15
]}

Gill, Devinder ^{[16
]}

Bloor, Adrian ^{[17
]}

Dearden, Claire ^{[18
]}

Moreno, Carol ^{[19
]}

Cull, Gavin ^{[20
]}

Hamblin, Mike ^{[21
]}

Jones, Jeffrey A. ^{[22
]}

Eckert, Karl ^{[23
]}

Solman, Isabelle G. ^{[23
]}

Suzuki, Samuel ^{[23
]}

Hsu, Emily ^{[23
]}

James, Danelle F. ^{[23
]}

Byrd, John C. ^{[22
]}

Hillmen, Peter ^{[24
]}

机构：

[1] Zucker Sch Med Hofstra Northwell, Lake Success, NY USA

[2] Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA USA

[3] Dana Farber Canc Inst, Boston, MA 02115 USA

[4] Mayo Clin, Rochester, MN USA

[5] Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[6] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[7] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia

[8] St Vincents Hosp, Melbourne, Vic, Australia

[9] Univ Sydney, Royal North Shore Hosp, Sydney, NSW, Australia

[10] Med Univ Vienna, Vienna, Austria

[11] NHS Fdn Trust, Kings Coll Hosp, London, England

[12] NHS Fdn Trust, East Kent Hosp Univ, Canterbury, Kent, England

[13] Med Univ Lodz, Lodz, Poland

[14] Perelman Ctr Adv Med, Philadelphia, PA USA

[15] Univ Oxford, Oxford Natl Inst Hlth Res Biomed Res Ctr, Oxford, England

[16] Princess Alexandra Hosp, Brisbane, Qld, Australia

[17] Christie Clin, Manchester, Lancs, England

[18] NHS Fdn Trust, Royal Marsden Hosp, London, England

[19] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[20] Sir Charles Gairdner Hosp, Nedlands, WA, Australia

[21] NHS Fdn Trust, Colchester Hosp, Colchester, Essex, England

[22] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA

[23] Pharmacycl LLC, Sunnyvale, CA USA

[24] St James Univ Hosp, Leeds Teaching Hosp, Leeds, W Yorkshire, England

来源：

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA | 2018年 / 18卷 / 12期

基金：

美国国家卫生研究院;

关键词：

Bruton's tyrosine kinase; Disease-related symptoms; Fatigue; Quality of life; Relapsed/refractory CLL/SLL; QUALITY-OF-LIFE; FLUDARABINE PLUS CYCLOPHOSPHAMIDE; INITIAL THERAPY; CHLORAMBUCIL; MULTICENTER; TRIAL;

D O I：

10.1016/j.clml.2018.08.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. 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 TherapyeFatigue (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. (C) 2018 The Authors. Published by Elsevier Inc.

引用

页码：803 / +

页数：18

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