Citation: British Journal of Haematology. 2019, 185(4), 656-69
Author: Eyre T.A. (toby.eyre@ouh.nhs.uk); Schuh A.H.; Kirkwood A.A.; Gohill S.; Follows G.; Walewska R.; Walter H.; Cross M.; Forconi F.; Shah N.; Chasty R.; Hart A.; Broom A.; Marr H.; Patten P.E.M.; Dann A.; Arumainathan A.; Munir T.; Shankara P.; Bloor A.; Johnston R.; Orchard K.; Fox C.P.
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.
© 2019 British Society for Haematology and John Wiley & Sons Ltd.
KEYWORDS: B cell receptor inhibitor, ibrutinib, idelalisib, p53 venetoclax; BCL2; chronic lymphocytic leukaemia
Link to PubMed record
