Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post‐BCRinhibitor setting: aUKwide analysis

Abstract

Summary 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.

The efficacy and safety of venetoclax therapy in elderly patients with relapsed, refractory chronic lymphocytic leukaemia

“…Recent large retrospective, multicentre series (Mato et al, ; Eyre et al, ) have demonstrated reassuringly similar efficacy and survival to trial outcomes. A toxicity analysis [including rates of tumour lysis syndrome (TLS), dose interruptions and discontinuations] has been assessed in a recent all‐age cohort (Roeker et al, ) but the specific question of efficacy and tolerability in elderly non‐trial patients has not been specifically addressed.…”

“…Recent large retrospective, multicentre series (Mato et al, 2018b;Eyre et al, 2019) interruptions and discontinuations] has been assessed in a recent all-age cohort (Roeker et al, 2019) but the specific question of efficacy and tolerability in elderly non-trial patients has not been specifically addressed.…”

Is venetoclax a new wonder drug in CLL?

“…Also, 29% of patients stopped the venetoclax therapy in the USA study (Mato et al , ) compared to only 8% in the study reported by Eyre et al (). Perhaps the lessons learned from the real‐world ibrutinib experience by UK clinicians led to the very impressive venetoclax results reported in this issue (Eyre et al , )?…”

“…A similar real-world study from the USA revealed a rather disappointing ORR of 72% but follow-up was very short at only 7 months and results may improve (Mato et al, 2018). Also, 29% of patients stopped the venetoclax therapy in the USA study (Mato et al, 2018) compared to only 8% in the study reported by Eyre et al (2019). Perhaps the lessons learned from the real-world ibrutinib experience by UK clinicians led to the very impressive venetoclax results reported in this issue (Eyre et al, 2019)?…”

“…In this issue of BJH, Eyre et al () undertook a similar UK retrospective real‐world analysis of venetoclax‐treated relapsed/refractory CLL patients, including many with 17p dysfunction (48%) and who had failed either a BTK inhibitor (60%), PI3K inhibitor (25%) or both therapies (10%), i.e. 85% had received a B‐cell receptor inhibitor (BCRi).…”