Obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) frontline treatment for high-risk chronic lymphocytic leukemia
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Despite considerable treatment advances with targeted therapies for patients with chronic lymphocytic leukemia (CLL) deemed high-risk [del(17p) and/or TP53 mutation], the outcome is still inferior compared with other CLL patients. Combining multiple agents with distinct mechanisms of action may further improve outcomes. CLL2-GIVe is an open-label, multicenter trial which enrolled patients with previously untreated CLL with del(17p) and/or TP53 mutation. Patients received induction therapy with obinutuzumab (GA-101), ibrutinib, and venetoclax (GIVe) for cycles 1 through 6 and consolidation therapy with venetoclax and ibrutinib for cycles 7 through 12. Ibrutinib monotherapy was continued for cycles 13 through 36 in patients not reaching a complete response (CR) with serial undetectable minimal residual disease (uMRD) after consolidation. The primary endpoint was CR rate at cycle 15 (final restaging). Secondary endpoints included MRD, survival, and safety. All 41 patients enrolled between September 2016 and August 2018 received study treatment and were included in efficacy and safety populations. With a CR rate of 58.5% at cycle 15, the primary endpoint was met (95% CI: 42.1-73.7; P < .001). At final restaging, 78.0% of patients had uMRD in peripheral blood (PB); 65.9% of patients had uMRD in bone marrow (BM). Estimated progression-free survival (PFS) and overall survival (OS) rates at 24 months were both 95.1%. Adverse events were reported in all patients; most were low grade (grade ≥3: 23.9%). Two deaths were reported (cardiac failure and ovarian carcinoma), neither related to study treatment. The CLL2-GIVe treatment regimen has a manageable safety profile and is a first-line treatment of good efficacy for patients with high-risk CLL.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Blood |
| Vol/bind | 139 |
| Udgave nummer | 9 |
| Sider (fra-til) | 1318-1329 |
| Antal sider | 12 |
| ISSN | 0006-4971 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
The authors wish to thank the patients and their families, the investigators at the sites, and the German CLL Study Group study office. We especially want to thank Michaela Grimm and Anke Hallmen of Ulm University Medical Center study office and the team of the German CLL Study Group central office at Cologne University Medical Center for their contribution to the conduct of the study. The trial design was developed by the German CLL Study Group, sponsor of the study was Ulm University Medical Center, and the study was supported by Roche Pharma AG and Janssen Cilag. Sponsor and German CLL Study Group representatives analyzed the data and wrote the first draft of the manuscript. Initial medical editing support was provided by Rachel Dobb and Lynda McEvoy of Ashfield MedComms, an Ashfield Health company.
Funding Information:
Conflict-of-interest disclosure: J.v.T.: research support: Janssen/Roche; travel grants: Abbvie, Janssen, Roche, Celgene; honoraria: Roche, Janssen, Abbvie, AstraZeneca; advisory boards: Janssen, Roche, Abbvie. H.H.: travel grants: Novartis; honoraria: Abbvie. P.D.: consultancy for AbbVie, AstraZeneca, Bluebird Bio, Gilead, Janssen, Novartis, Riemser, and Roche; speakers bureau for AbbVie, AstraZeneca, Gilead, Novartis, Riemser, and Roche. S.B.: payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: Roche, AbbVie, Norvatis, Becton Dickinson, Janssen, Astra Zeneca, and Sanofi; grants or contracts from any entity: Janssen Cilag Neuss. A.-M.F.: research funding: Celgene; advisory board: Janssen; and travel grants: AbbVie. C.U.N.: grant research: Abbvie, Janssen, and AstraZeneca; advisory board: Abbvie, Janssen, Gilead, Roche, AstraZeneca, Acerta, and Sunsis; travel reimbursement: Gilead, Roche, Novartis; consultancy: CSL Behring. S.S.: advisory board honoraria, research support, travel support, speaker fees: AbbVie, Amgen, AstraZeneca, Celgene, Gilead, GSK, Hoffmann-La Roche, Janssen, Novartis, and Sunesis. All other authors declare no competing financial interests.
Publisher Copyright:
© 2022 American Society of Hematology
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