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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
Author(s) -
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.,
Fox Christopher P.
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15802
Subject(s) - venetoclax , discontinuation , medicine , hazard ratio , gastroenterology , tumor lysis syndrome , refractory (planetary science) , progression free survival , chronic lymphocytic leukemia , chemotherapy , oncology , leukemia , confidence interval , biology , astrobiology
Summary Venetoclax is a BCL 2 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 TP 53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor ( BTK i) and no prior phosphoinositide 3‐kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTK i, and 10% received both. Patients discontinued B cell receptor inhibitor ( BCR i) 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 BTK i‐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 BCR i 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 BCR i. Reason(s) for stopping BCR i influences venetoclax outcomes.