Efficacy of venetoclax monotherapy in patients with relapsed CLL in the post‐BCR inhibitor setting: a UK wide analysis

[Jm954]

Feb 2019

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.

Ref here (but no additional information): onlinelibrary.wiley.com/doi...

Jackie

[GrapeGrower1]

If overall survival was 75.0, these patients must have been in last resort status?

[Jm954 Administrator in reply to GrapeGrower1]

Yes, probably for the people who progressed on a BCRi.

Quote: 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)

Jackie