Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study

Peter Hillmen, Andy C Rawstron, Kristian Brock, Sam Munoz Vicente, Frankie Yates, Rebecca Bishop, Becky Boucher, Donald McDonald, Chris Fegan, Alison McCaig, Anna Schuh, Andrew Pettitt, John Gribben, Piers Patten, Stephen Devereux, Adrian Bloor, Christopher Fox, Francesco Forconi, Talha Munir

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PURPOSE: The treatment of chronic lymphocytic leukemia (CLL) has been revolutionized by targeted therapies that either inhibit proliferation (ibrutinib) or reactivate apoptosis (venetoclax). Both significantly improve survival in CLL and replace chemoimmunotherapy for many patients. However, individually, they rarely lead to eradication of measurable residual disease (MRD) and usually are taken indefinitely or until progression. We present the CLARITY trial that combined ibrutinib with venetoclax to eradicate detectable CLL with the intention of stopping therapy.

PATIENTS AND METHODS: CLARITY is a phase II trial that combined ibrutinib with venetoclax in patients with relapsed or refractory CLL. The primary end point was eradication of MRD after 12 months of combined therapy. Key secondary end points were response by International Workshop on CLL criteria, safety, and progression-free and overall survival.

RESULTS: In 53 patients after 12 months of ibrutinib plus venetoclax, MRD negativity (fewer than one CLL cell in 10,000 leukocytes) was achieved in the blood of 28 (53%) and the marrow of 19 (36%). Forty-seven patients (89%) responded, and 27 (51%) achieved a complete remission. After a median follow-up of 21.1 months, one patient progressed, and all patients were alive. A single case of biochemical tumor lysis syndrome was observed. Other adverse effects were mild and/or manageable and most commonly were neutropenia or GI events.

CONCLUSION: The combination of ibrutinib plus venetoclax was well tolerated in patients with relapsed or refractory CLL. There was a high rate of MRD eradication that led to the cessation of therapy in some patients. The progression-free and overall survival rates are encouraging for relapsed and refractory CLL.
Original languageEnglish
Pages (from-to)2722-2729
Number of pages8
JournalJournal of Clinical Oncology
Issue number30
Early online date11 Jul 2019
Publication statusPublished - 20 Oct 2019


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