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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

Eyre, TA; Kirkwood, AA; Gohill, S; Follows, G; Walewska, R; Walter, H; Cross, M; ... the UK CLL Forum, ; + view all (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 , 185 (4) pp. 656-669. 10.1111/bjh.15802.

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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.

Type: Article
Title: Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis
Location: England
DOI: 10.1111/bjh.15802
Publisher version: https://doi.org/10.1111/bjh.15802
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: B cell receptor inhibitor, ibrutinib, idelalisib, p53 venetoclax, BCL2, chronic lymphocytic leukaemia
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10077738
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