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Clinical Trial
. 2019 Oct 20;37(30):2722-2729.
doi: 10.1200/JCO.19.00894. Epub 2019 Jul 11.

Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study

Peter Hillmen  1   2 , Andy C Rawstron  2 , Kristian Brock  3 , Samuel Muñoz-Vicente  3 , Francesca J Yates  3 , Rebecca Bishop  3 , Rebecca Boucher  3 , Donald MacDonald  4 , Christopher Fegan  5   6 , Alison McCaig  7 , Anna Schuh  8 , Andrew Pettitt  9 , John G Gribben  10 , Piers E M Patten  11   12 , Stephen Devereux  11 , Adrian Bloor  13 , Christopher P Fox  14 , Francesco Forconi  15   16 , Talha Munir  2
Affiliations
Clinical Trial

Ibrutinib Plus Venetoclax in Relapsed/Refractory Chronic Lymphocytic Leukemia: The CLARITY Study

Peter Hillmen et al. J Clin Oncol. .

Erratum in

  • Errata.
    [No authors listed] [No authors listed] J Clin Oncol. 2020 May 10;38(14):1644. doi: 10.1200/JCO.20.00411. J Clin Oncol. 2020. PMID: 32375017 Free PMC article. No abstract available.

Abstract

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.

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Figures

FIG 1.
FIG 1.
Dynamic of response. CLL, chronic lymphocytic leukemia.
FIG 2.
FIG 2.
Peripheral blood and bone marrow responses with time. MRD3, fewer than one CLL cell in 1,000 leukocytes; MRD4, measurable residual disease to fewer than one chronic lymphocytic leukemia cell in 10,000 leukocytes; MRD5, residual disease undetectable below a threshold of one CLL cell in 100,000 leukocytes; NA, not available.
See this image and copyright information in PMC

Comment in

References

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