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Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: The CLARITY Study

Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: The CLARITY Study
Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: The CLARITY Study

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.

1527-7755
2722-2729
Hillmen, Peter
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Rawstron, Andy C.
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Brock, Kristian
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Muñoz-Vicente, Samuel
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Yates, Francesca J.
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Bishop, Rebecca
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Boucher, Rebecca
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MacDonald, Donald
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Fegan, Christopher
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McCaig, Alison
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Schuh, Anna
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Pettitt, Andrew
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Gribben, John G.
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Patten, Piers E.M.
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Devereux, Stephen
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Bloor, Adrian
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Fox, Christopher P.
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Forconi, Francesco
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Munir, Talha
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Hillmen, Peter
ab511e8c-32e6-44f3-9653-bea4e967de8d
Rawstron, Andy C.
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Brock, Kristian
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Muñoz-Vicente, Samuel
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Yates, Francesca J.
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Bishop, Rebecca
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Boucher, Rebecca
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MacDonald, Donald
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Fegan, Christopher
4af7695c-6da8-4348-b5ec-61da967aa9da
McCaig, Alison
602f4631-c4df-455e-b884-99e8d1475b13
Schuh, Anna
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Pettitt, Andrew
fb9da802-0ff6-420d-8805-0efb461f823d
Gribben, John G.
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Patten, Piers E.M.
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Devereux, Stephen
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Bloor, Adrian
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Fox, Christopher P.
fc503642-a38b-4b7c-ab80-126d2c522f74
Forconi, Francesco
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Munir, Talha
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Hillmen, Peter, Rawstron, Andy C., Brock, Kristian, Muñoz-Vicente, Samuel, Yates, Francesca J., Bishop, Rebecca, Boucher, Rebecca, MacDonald, Donald, Fegan, Christopher, McCaig, Alison, Schuh, Anna, Pettitt, Andrew, Gribben, John G., Patten, Piers E.M., Devereux, Stephen, Bloor, Adrian, Fox, Christopher P., Forconi, Francesco and Munir, Talha (2019) Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: The CLARITY Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37 (30), 2722-2729. (doi:10.1200/JCO.19.00894).

Record type: Article

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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Accepted/In Press date: 31 May 2019
e-pub ahead of print date: 11 July 2019
Published date: 20 October 2019

Identifiers

Local EPrints ID: 435042
URI: http://eprints.soton.ac.uk/id/eprint/435042
ISSN: 1527-7755
PURE UUID: c3fb20cf-9f8a-4c4d-b266-f7bf0ba10ecf

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Date deposited: 18 Oct 2019 16:30
Last modified: 25 Nov 2021 22:48

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Contributors

Author: Peter Hillmen
Author: Andy C. Rawstron
Author: Kristian Brock
Author: Samuel Muñoz-Vicente
Author: Francesca J. Yates
Author: Rebecca Bishop
Author: Rebecca Boucher
Author: Donald MacDonald
Author: Christopher Fegan
Author: Alison McCaig
Author: Anna Schuh
Author: Andrew Pettitt
Author: John G. Gribben
Author: Piers E.M. Patten
Author: Stephen Devereux
Author: Adrian Bloor
Author: Christopher P. Fox
Author: Talha Munir

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