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Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis

Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis
Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis

Venetoclax is a BCL2 inhibitor with activity in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). We conducted a multi-centre retrospective analysis of 105 R/R CLL patients who received venetoclax pre-National Health Service commissioning. The median age was 67 years and median prior lines was 3 (range: 1–15). 48% had TP53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor (BTKi) and no prior phosphoinositide 3-kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTKi, and 10% received both. Patients discontinued B cell receptor inhibitor (BCRi) because of toxicity in 44% and progression in 54%. Tumour lysis syndrome risk was low, intermediate or high in 27%, 25%, and 48% respectively. Overall response was 88% (30% complete response [CR]). The overall response rate was 85% (CR 23%) in BTKi-exposed patients, 92% (CR 38%) in Pi3Ki-exposed patients and 80% (CR 20%) in both (P = 0·59). With a median follow-up of 15·6 months, 1-year progression-free survival was 65·0% and 1-year overall survival was 75·1%. Dose reduction or temporary interruption did not result in an inferior progression-free or discontinuation-free survival. Risk of progression or death after stopping a prior BCRi for progression was double compared to those stopping for other reasons (predominantly toxicity) (Hazard Ratio 2·01 P = 0·05). Venetoclax is active and well tolerated in R/R CLL post ≥1 BCRi. Reason(s) for stopping BCRi influences venetoclax outcomes.

B cell receptor inhibitor, ibrutinib, idelalisib, p53 venetoclax, BCL2, chronic lymphocytic leukaemia
0007-1048
Eyre, Toby A.
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Kirkwood, Amy A.
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Gohill, Sat
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Follows, George
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Walewska, Renata
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Walter, Harriet
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Cross, Matthew
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Forconi, Francesco
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Shah, Nimish
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Chasty, Richard
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Hart, Alistair
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Broom, Angus
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Marr, Helen
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Patten, Piers E.M.
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Dann, Andy
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Arumainathan, Arvind
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Munir, Tal
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Shankara, Paneesha
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Bloor, Adrian
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Johnston, Rosalynd
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Orchard, Kim
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Schuh, Anna H.
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Fox, Christopher P.
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the UK CLL Forum
Eyre, Toby A.
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Kirkwood, Amy A.
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Gohill, Sat
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Follows, George
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Walewska, Renata
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Walter, Harriet
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Cross, Matthew
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Forconi, Francesco
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Shah, Nimish
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Chasty, Richard
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Hart, Alistair
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Broom, Angus
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Marr, Helen
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Patten, Piers E.M.
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Dann, Andy
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Arumainathan, Arvind
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Munir, Tal
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Shankara, Paneesha
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Bloor, Adrian
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Johnston, Rosalynd
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Orchard, Kim
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Schuh, Anna H.
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Fox, Christopher P.
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Eyre, Toby A., Kirkwood, Amy A., Gohill, Sat, Follows, George, Walewska, Renata, Walter, Harriet, Cross, Matthew, Forconi, Francesco, Shah, Nimish, Chasty, Richard, Hart, Alistair, Broom, Angus, Marr, Helen, Patten, Piers E.M., Dann, Andy, Arumainathan, Arvind, Munir, Tal, Shankara, Paneesha, Bloor, Adrian, Johnston, Rosalynd, Orchard, Kim, Schuh, Anna H. and Fox, Christopher P. , the UK CLL Forum (2019) Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis. British Journal of Haematology. (doi:10.1111/bjh.15802).

Record type: Article

Abstract

Venetoclax is a BCL2 inhibitor with activity in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). We conducted a multi-centre retrospective analysis of 105 R/R CLL patients who received venetoclax pre-National Health Service commissioning. The median age was 67 years and median prior lines was 3 (range: 1–15). 48% had TP53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor (BTKi) and no prior phosphoinositide 3-kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTKi, and 10% received both. Patients discontinued B cell receptor inhibitor (BCRi) because of toxicity in 44% and progression in 54%. Tumour lysis syndrome risk was low, intermediate or high in 27%, 25%, and 48% respectively. Overall response was 88% (30% complete response [CR]). The overall response rate was 85% (CR 23%) in BTKi-exposed patients, 92% (CR 38%) in Pi3Ki-exposed patients and 80% (CR 20%) in both (P = 0·59). With a median follow-up of 15·6 months, 1-year progression-free survival was 65·0% and 1-year overall survival was 75·1%. Dose reduction or temporary interruption did not result in an inferior progression-free or discontinuation-free survival. Risk of progression or death after stopping a prior BCRi for progression was double compared to those stopping for other reasons (predominantly toxicity) (Hazard Ratio 2·01 P = 0·05). Venetoclax is active and well tolerated in R/R CLL post ≥1 BCRi. Reason(s) for stopping BCRi influences venetoclax outcomes.

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VEN CLL - Accepted Manuscript
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Accepted/In Press date: 2 January 2019
e-pub ahead of print date: 15 February 2019
Keywords: B cell receptor inhibitor, ibrutinib, idelalisib, p53 venetoclax, BCL2, chronic lymphocytic leukaemia

Identifiers

Local EPrints ID: 428925
URI: https://eprints.soton.ac.uk/id/eprint/428925
ISSN: 0007-1048
PURE UUID: 1c071d7f-c9e9-4c92-940f-219b9e35806a
ORCID for Kim Orchard: ORCID iD orcid.org/0000-0003-2276-3925

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Date deposited: 14 Mar 2019 17:30
Last modified: 15 Mar 2019 01:35

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Contributors

Author: Toby A. Eyre
Author: Amy A. Kirkwood
Author: Sat Gohill
Author: George Follows
Author: Renata Walewska
Author: Harriet Walter
Author: Matthew Cross
Author: Nimish Shah
Author: Richard Chasty
Author: Alistair Hart
Author: Angus Broom
Author: Helen Marr
Author: Piers E.M. Patten
Author: Andy Dann
Author: Arvind Arumainathan
Author: Tal Munir
Author: Paneesha Shankara
Author: Adrian Bloor
Author: Rosalynd Johnston
Author: Kim Orchard ORCID iD
Author: Anna H. Schuh
Author: Christopher P. Fox

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