Department of Haematology, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Cancer Research UK & UCL Cancer Trials Centre, UCL, London, UK.
Br J Haematol. 2019 May;185(4):656-669. doi: 10.1111/bjh.15802. Epub 2019 Feb 15.
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.
维奈托克是一种 BCL2 抑制剂，对复发/难治性（R/R）慢性淋巴细胞白血病（CLL）有活性。我们对 105 名在国家卫生服务机构委托前接受维奈托克治疗的 R/R CLL 患者进行了一项多中心回顾性分析。中位年龄为 67 岁，中位既往线数为 3（范围：1-15）。48%的患者存在 TP53 缺失。在≥2 线治疗中，60%的患者接受了布鲁顿酪氨酸激酶抑制剂（BTKi），而没有接受过磷酸肌醇 3-激酶抑制剂（Pi3Ki），25%的患者接受了 Pi3Ki，而没有接受过 BTKi，10%的患者同时接受了两种药物。由于毒性，44%的患者停止了 B 细胞受体抑制剂（BCRi）治疗，由于疾病进展，54%的患者停止了 BCRi 治疗。肿瘤溶解综合征风险分别为低危、中危和高危，占比分别为 27%、25%和 48%。总缓解率为 88%（30%完全缓解[CR]）。在接受过 BTKi 治疗的患者中，总缓解率为 85%（CR 为 23%），在接受过 Pi3Ki 治疗的患者中，总缓解率为 92%（CR 为 38%），在同时接受两种药物治疗的患者中，总缓解率为 80%（CR 为 20%）（P=0.59）。中位随访 15.6 个月时，1 年无进展生存率为 65.0%，1 年总生存率为 75.1%。剂量减少或临时中断不会导致无进展或停药生存时间降低。与因其他原因（主要是毒性）停药的患者相比，因疾病进展而停止先前 BCRi 治疗的患者进展或死亡的风险增加了一倍（风险比 2.01，P=0.05）。维奈托克在接受过≥1 种 BCRi 治疗的 R/R CLL 患者中具有活性且耐受良好。停止 BCRi 的原因影响维奈托克的治疗结局。
