Single-agent ibrutinib versus chemoimmunotherapy regimens for treatment-naïve patients with chronic lymphocytic leukemia : A cross-trial comparison of phase 3 studies
Robak, Tadeusz (Medical University of Lodz)
Burger, Jan A. (The University of Texas MD Anderson Cancer Center)
Tedeschi, Alessandra (ASST Grande Ospedale Metropolitano Niguarda)
Barr, Paul M. (University of Rochester Cancer Center)
Owen, Carolyn (University of Calgary)
Bairey, Osnat (Tel Aviv University)
Hillmen, Peter (St. James's Institute of Oncology)
Simpson, David (North Shore Hospital)
Grosicki, Sebastian (Silesian Medical University)
Devereux, Stephen (King's College Hospital NHS Foundation Trust)
McCarthy, Helen (Royal Bournemouth Hospital)
Coutre, Steven E (Stanford University School of Medicine)
Quach, Hang (St. Vincent's Hospital)
Gaidano, Gianluca (Amedeo Avogadro University of Eastern Piedmont)
Maslyak, Zvenyslava (Institute of Blood Pathology and Transfusion Medicine of the Academy of Medical Sciences of Ukraine)
Stevens, Don A. (Norton Cancer Institute)
Moreno, Carol (Institut d'Investigació Biomèdica Sant Pau)
Gill, Devinder S. (Princess Alexandra Hospital)
Flinn, Ian W. (Sarah Cannon Research Institute/Tennessee Oncology)
Gribben, John G. (Queen Mary University of London)
Mokatrin, Ahmad (Pharmacyclics LLC. an AbbVie Company)
Cheng, Mei (Pharmacyclics LLC. an AbbVie Company)
Styles, Lori (Pharmacyclics LLC. an AbbVie Company)
James, Danelle F. (Pharmacyclics LLC. an AbbVie Company)
Kipps, Thomas J (University of California San Diego)
Ghia, Paolo (Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele)
Universitat Autònoma de Barcelona

Date:	2018
Abstract:	Chemoimmunotherapy (CIT) and targeted therapy with single-agent ibrutinib are both recommended first-line treatments for chronic lymphocytic leukemia (CLL), although their outcomes have not been directly compared. Using ibrutinib data from the RESONATE-2 (PCYC-1115/1116) study conducted in patients ≥65 years without del(17p), we performed a cross-trial comparison with CIT data from published phase 3 studies in first-line treatment of CLL. Progression-free survival (PFS), overall survival (OS), and safety data for ibrutinib (median follow-up 35. 7 months) were evaluated alongside available CIT data. CIT regimens included: fludarabine + cyclophosphamide + rituximab (CLL8, CLL10), bendamustine + rituximab (CLL10), obinutuzumab + chlorambucil and rituximab + chlorambucil (CLL11), and ofatumumab + chlorambucil (COMPLEMENT-1). Median age across studies was 61-74 years, with older populations receiving ibrutinib, obinutuzumab + chlorambucil, or rituximab + chlorambucil. Median follow-up varied across studies/regimens (range 14. 5-37. 4 months). Among all patients, PFS appeared longer with ibrutinib relative to CIT and OS appeared comparable. Relative to CIT studies that similarly excluded patients with del(17p) (CLL10) or enrolled older/less-fit patients (CLL11), PFS appeared favorable for ibrutinib in high-risk subgroups, including advanced disease, bulky lymph nodes, unmutated IGHV status, and presence of del(11q). Grade ≥ 3 infections ranged from 9% (ofatumumab + chlorambucil) to 40% (fludarabine + cyclophosphamide + rituximab), and was 25% with ibrutinib. Grade ≥ 3 neutropenia was 12% for ibrutinib and 26%-84% for CIT. Although definitive conclusions cannot be made due to inherent limitations of cross-trial comparisons, this report suggests that ibrutinib has a favorable benefit/risk profile and may potentially eliminate the need for chemotherapy in some patients. Randomized, comparative studies are needed to support these findings.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	American Journal of Hematology, Vol. 93 Núm. 11 (november 2018) , p. 1402-1410, ISSN 1096-8652

DOI: 10.1002/ajh.25259
PMID: 30129285

9 p, 1.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles