First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial
iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or <65 years with...
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| Vydané v: | Haematologica (Roma) Ročník 107; číslo 9; s. 2108 - 2120 |
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| Hlavní autori: | , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
Italy
Fondazione Ferrata Storti
01.09.2022
Ferrata Storti Foundation |
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| ISSN: | 0390-6078, 1592-8721, 1592-8721 |
| On-line prístup: | Získať plný text |
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| Shrnutí: | iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or <65 years with coexisting conditions. Patients received oral ibrutinib 420 mg once daily until disease progression or unacceptable toxicity or six cycles of oral chlorambucil, each in combination with six cycles of intravenous obinutuzumab. After a median follow-up of 45 months (range, 0.2-52), median progression-free survival continued to be significantly longer in the ibrutinib plus obinutuzumab arm than in the chlorambucil plus obinutuzumab arm (median not reached versus 22 months; hazard ratio=0.25; 95% confidence interval: 0.16-0.39; P<0.0001). The best overall rate of undetectable minimal residual disease (<0.01% by flow cytometry) remained higher with ibrutinib plus obinutuzumab (38%) than with chlorambucil plus obinutuzumab (25%). With a median treatment duration of 42 months, 13 months longer than the primary analysis, no new safety signals were identified for ibrutinib. As is typical for ibrutinib-based regimens, common grade ≥3 adverse events were most prevalent in the first 6 months of ibrutinib plus obinutuzumab treatment and generally decreased over time, except for hypertension. In this final analysis with up to 52 months of follow-up (median 45 months), ibrutinib plus obinutuzumab showed sustained clinical benefit, in terms of progression- free survival, in first-line treatment of chronic lymphocytic leukemia, including in patients with high-risk features. ClinicalTrials.gov identifier: NCT02264574. |
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| Bibliografia: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 Disclosures CM has provided consulting/advisory services for Janssen, AbbVie, AstraZeneca, and BeiGene; has received research funding from AbbVie and Janssen; and participated in speakers bureaus for AbbVie and Janssen. RG has received honoraria from Celgene, Roche, Merck, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, AbbVie, Gilead, and Daiichi Sankyo; has provided consulting/advisory services for Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, AbbVie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankyo; has received research funding from Celgene, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Gilead, and Roche; has received travel or accommodation funds from Roche, Amgen, Janssen, AstraZeneca, Novartis, Merck Sharp & Dohme, Celgene, Gilead, Bristol Myers Squibb, and AbbVie. FD has had a consulting/advisory role for AbbVie, AstraZeneca, Roche, and Amgen; has received research funding from AbbVie, Janssen, Pharmacyclics LLC, an AbbVie company, and AstraZeneca; has participated in speakers bureaus for Janssen, AbbVie, and Amgen; and has received travel or accommodation expenses from Amgen, Janssen, AbbVie, and Pfizer. AT has received honoraria from Janssen, AbbVie, AstraZeneca, and BeiGene; and has participated in speakers bureaus for Janssen, BeiGene, AstraZeneca, and AbbVie. BA has nothing to disclose. LL has provided consulting/advisory services for AbbVie and Janssen. MS has received honoraria from AbbVie, Roche, Janssen-Cilag, Gilead, and Acerta Pharma; has played a consulting/advisory role for AbbVie; has participated in speakers bureaus for AbbVie, Roche, Janssen-Cilag, and Gilead; and has received travel or accommodation expenses from AbbVie, Roche, Janssen-Cilag, and Gilead. JN has played a consulting/advisory role for Amgen, Takeda, Roche, Celgene, Pfizer, and Novartis; and has received travel or accommodation expenses from Amgen and Janssen. VS is employed by Eco-Safety Medical Center; has stock ownership in Portola Pharmaceuticals, Gilead, Moderna, and Clovis Oncology; has received research funding from Janssen; and has received travel or accommodation expenses from AbbVie and Janssen. DG has received honoraria from Janssen-Cilag; and has played a consulting/advisory role for Janssen-Cilag. JGG has received honoraria from AbbVie, Roche, Bristol Myers Squibb, Janssen, and AstraZeneca; has provided consulting/advisory services for AbbVie, Janssen, and Gilead; and received research funding from Janssen, AstraZeneca, and Celgene. KK is employed by Pharmacyclics LLC, an AbbVie Company; and owns stock in Pharmacyclics LLC, an AbbVie Company, and Gilead. SD has been employed by Pharmacyclics LLC, an AbbVie Company. and Horizon Therapeutics; and has stock ownership in AbbVie, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Exelixis, Revance, Horizon Therapeutics, and Myovant Science. EH and JPD are employed by Pharmacyclics LLC, an AbbVie Company; and own stock in AbbVie. IWF has provided consulting/advisory services for AbbVie, AstraZeneca, BeiGene, Genentech, Gilead, Great Point Partners, Iksuda Therapeutics, Janssen, Juno Therapeutics, Kite Pharma, MorphoSys, Nurix Therapeutics, Pharmacyclics LLC, an AbbVie Company, Roche, Seattle Genetics, Takeda, TG Therapeutics, Unum Therapeutics, Verastem, and Yingli Pharma; and has received research funding from AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Curis, Forma Therapeutics, Forty Seven, Genentech, Gilead, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Janssen, Juno Therapeutics, Karyopharm Therapeutics, Kite Pharma, Loxo, Merck, MorphoSys, Novartis, Pfizer, Pharmacyclics LLC, an AbbVie Company, Portola Pharmaceuticals, Rhizen Pharmaceuticals, Roche, Seattle Genetics, Takeda, Teva, TG Therapeutics, Trillium Therapeutics, Triphase Pharma, Unum Therapeutics, and Verastem. Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu. Contributions As members of the Steering Committee, CM, DG, JGG, and IWF collaborated with the study sponsors to design the study and protocol; CM, RG, RD, AT, BA, LL, MS, JN, VS, DG, JGG, and IWF collected the study data; SD analyzed the data; KK collected and tested the high-risk genomic factor data for the study; SD, EH, and JD confirmed the accuracy of the data and compiled it for analysis. All authors had access to the data and were involved in the interpretation of data, contributed to the manuscript review and revisions, and approved the final version for submission. Data-sharing statement |
| ISSN: | 0390-6078 1592-8721 1592-8721 |
| DOI: | 10.3324/haematol.2021.279012 |