A new study from the UK Chronic Lymphocytic Leukaemia (CLL) Forum has found that venetoclax is active and well-tolerated in relapsed/refractory (R/R) CLL after at least one bruton tyrosine kinase inhibitor (BTKi). However, outcomes are influenced by the reasons for B cell receptor inhibitor (BCRi) discontinuation.
The multi-centre retrospective study analysed data from 105 patients with R/R CLL who received venetoclax prior to NHS commissioning. The median number of prior treatment lines was three, although the range extended from one to 15. Of the cohort, 48% had TP53 disruption.
Among those who received at least two prior lines of treatment, 60% received a BTKi and no prior phosphoinositide 3-kinase inhibitor (Pi3Ki); 25% received a Pi3Ki and no prior BTKi; and 10% received both.
Discontinuation of BCRi therapy was attributed to toxicity in 44% of cases and to progression in 54% of patients.
Overall response rate (ORR) with venetoclax was 88%, with a complete response rate of 30%. ORR was 85% in BTKi-exposed patients, 92% in Pi3Ki-exposed patients, and 80% in patients who received both (P=0.59). Complete response rates were 23%, 38%, and 20%, respectively.
At a median follow-up of 15.6 months, one-year progression-free survival (PFS) was 65% and one-year overall survival was 75.1%. Dose reduction or temporary interruption did not result in inferior PFS or discontinuation-free survival.
Risk of progression or death after stopping a prior BCRi because of progression was double compared to those stopping for other reasons (predominantly toxicity) (HR 2.01; P=0.05).
