Venetoclax-Dexamethasone Versus Pomalidomide-Dexamethasone in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma: Primary Results of the Randomized, Phase III CANOVA Study.

Methods

The randomized, open-label, phase III CANOVA study (ClinicalTrials.gov identifier: NCT03539744) enrolled adults with t(11;14)-positive RRMM who had received ≥2 previous lines of therapy.

随机、开放标签、III期CANOVA研究（ClinicalTrials.gov注册号：NCT03539744）招募了接受≥2线先前治疗的t(11;14)阳性RRMM成人患者。

Patients were randomly assigned (1:1) to venetoclax-dexamethasone or pomalidomide-dexamethasone until progression or intolerable toxicity.

患者被随机分配（1:1）至维奈克拉-地塞米松组或泊马度米-地塞米松组，直至疾病进展或出现无法耐受的毒性。

The primary end point was independent review committee assessed-progression-free survival(PFS) in the intention-to-treatpopulation analyzed by stratified log-rank test (two-sided type I error rate, α = .05), with hazard ratio(HR) and 95% CI estimated by stratified Cox proportional hazard model.

主要终点是独立评审委员会评估的无进展生存期（PFS），在按意向治疗人群进行分析，采用分层的对数秩检验（双侧第一类错误率，α = .05），并通过分层的Cox比例风险模型估计风险比（HR）和95%置信区间。

Secondary end points included response rates, overall survival(OS), minimal residual disease (MRD) negativity rate (<10-5), and safety.

次要终点包括反应率、总生存（OS）、最小残留病（MRD）阴性率（<10^-5）和安全性。

Results

Overall, 263 patients were randomly assigned (venetoclax-dexamethasone, n = 133; pomalidomide-dexamethasone, n = 130).

总体而言，263名患者被随机分配（维奈克拉-地塞米松，n=133；泊马度米-地塞米松，n=130）。

Median PFS was 9.9 months (95% CI, 6.9 to 12.6) with venetoclax-dexamethasone versus 5.8 months (95% CI, 3.8 to 9.2) with pomalidomide-dexamethasone (HR, 0.823 [95% CI, 0.596 to 1.136]; P = .24).

中位无进展生存期（PFS）为9.9个月（95% 置信区间，6.9至12.6个月）使用维奈克拉-地塞米松治疗，而使用泊马度米-地塞米松治疗为5.8个月（95% 置信区间，3.8至9.2个月）（风险比，0.823 [95% 置信区间，0.596至1.136]；P = .24）。

Overall response and very good partial response or better rates were 62% and 39%, respectively, with venetoclax-dexamethasone versus 35% and 14% with pomalidomide-dexamethasone.

使用维奈克拉-地塞米松治疗的总缓解率和非常好的部分缓解或更好率分别为62%和39%，而使用泊马度米-地塞米松治疗的相应数据分别为35%和14%。

MRD negativity rate was 8% with venetoclax-dexamethasone and 0% with pomalidomide-dexamethasone.

MRD阴性率在使用维奈克拉-地塞米松治疗组为8%，而在使用泊马度米-地塞米松治疗组为0%。

Median OS was 32.4 months (95% CI, 26.4 to 40.7) with venetoclax-dexamethasone and 26.9 months (95% CI, 20.4 to 38.9) with pomalidomide-dexamethasone (HR, 0.856 [95% CI, 0.612 to 1.197]).

使用维奈克拉-地塞米松治疗的中位总生存期为32.4个月（95%置信区间，26.4至40.7个月），而使用泊马度米-地塞米松治疗的中位总生存期为26.9个月（95%置信区间，20.4至38.9个月）（风险比，0.856 [95%置信区间，0.612至1.197]）。

Grade ≥3 treatment-emergent adverse eventrates were 67% with venetoclax-dexamethasone versus 83% with pomalidomide-dexamethasone.

在接受维奈克拉-地塞米松治疗的患者中，3级或以上治疗相关不良事件的发生率为67%，而在接受泊马度胺-地塞米松治疗的患者中，这一比例为83%。

There were 16 (12%) treatment-emergent deaths with venetoclax-dexamethasone versus 8 (6%) with pomalidomide-dexamethasone.

维奈克拉-地塞米松治疗组出现了16例（12%）治疗相关死亡，相比之下，泊马度胺-地塞米松治疗组则有8例（6%）治疗相关死亡。

Conclusions

The primary end point of PFS was not met.

PFS的主要终点未达成。

PFS and OS were numerically longer with venetoclax-dexamethasone versus pomalidomide-dexamethasone in t(11;14)-positive RRMM.

在t(11;14)阳性复发/难治性多发性骨髓瘤患者中，与泊马度胺-地塞米松相比，维奈克拉-地塞米松治疗组的无进展生存期（PFS）和总生存期（OS）数值上更长。

Consistent with previous studies, infections were associated with venetoclax-dexamethasone; no new safety signals were observed.

与先前的研究一致，感染与维奈克拉-地塞米松相关；未观察到新的安全信号。