Venetoclax combinations in untreated CLL: 5-year results and patient-reported outcomes analysis of the CLL13/GAIA trial.

The phase 3 CLL13/GAIA trial assesses 3 time-limited combinations: venetoclax-rituximab (RV), venetoclax-obinutuzumab (GV), and venetoclax-obinutuzumab-ibrutinib (GIV), in comparison with chemoimmunotherapy (CIT).

第3阶段CLL13/GAIA试验评估了3种限时联合方案：维奈克拉-利妥昔单抗（RV）、维奈克拉-奥布妥珠单抗（GV）和维奈克拉-奥布妥珠单抗-伊布替尼（GIV），与化疗免疫治疗（CIT）进行比较。

Fit patients with CLL without TP53 aberrations were randomized between 6 cycles of CIT (fludarabine-cyclophosphamide-rituximab [FCR] or bendamustine-rituximab [BR]) or 12 cycles of RV, GV, or GIV (GIV: ibrutinib continuation until cycle 36 if measurable residual disease at months 12/15).

适合的慢性淋巴细胞白血病（CLL）患者，没有TP53异常，被随机分配接受6个周期的CIT（氟达拉滨-环磷酰胺-利妥昔单抗[FCR]或苯达莫司汀-利妥昔单抗[BR]）或12个周期的RV、GV或GIV治疗（GIV：如果在第12/15个月有可测量的残留疾病，则继续使用伊布替尼直至第36个周期）。

In total, 926 patients were randomized (GIV: 231, GV: 229, RV: 237, and CIT: 229 [FCR: 150, BR: 79]).

总共有926名患者被随机分配（GIV：231名，GV：229名，RV：237名，CIT：229名[FCR：150名，BR：79名]）。

With a median observation time of 63.8 months, 5-year progression-free survival(PFS) rates were 81.3% (GIV), 69.8% (GV), 57.4% (RV), and 50.7% (CIT).

中位观察时间为63.8个月，5年无进展生存（PFS）率分别为：GIV组81.3%，GV组69.8%，RV组57.4%，CIT组50.7%。

PFS was superior for GV and GIV compared with CIT and RV (P< .001 in each case).

与CIT和RV相比，GV和GIV的PFS更优（每个案例P< .001）。

In addition, GIV showed longer PFS than GV (P = .0046).

此外，GIV显示出比GV更长的无进展生存期（P = .0046）。

Venetoclax-based re-treatment after venetoclax-based first-line regimens was efficacious, with 2-year treatment-free survival >80% from second-line treatment.

在基于维奈克拉的首次治疗方案后，基于维奈克拉的再次治疗是有效的，从二线治疗开始的2年无治疗生存率超过80%。

No differences in overall survivalwere observed between treatment arms (5-year rates: GIV, 94.3%; GV, 93.6%; RV, 94.7%; and CIT, 90.7%).

治疗组之间的总生存率没有观察到差异（5年率：GIV，94.3%；GV，93.6%；RV，94.7%；CIT，90.7%）。

The incidencerates of severe infections were highest with CIT, whereas cardiac events were most frequent with GIV.

严重感染的发生率在CIT组中最高，而心脏事件在GIV组中最频繁。

Compared with patients treated with CIT, those treated with GV or RV reported rapid and significantly greater quality-of-life (QoL) improvements.

与接受CIT治疗的患者相比，接受GV或RV治疗的患者报告了更快且显著更大的生活质量(QoL)改善。

In the GIV arm, clinically relevant QoL improvements occurred later (month 15, after the end of treatment in most patients) than with GV/RV, likely due to a higher treatment-related symptom burden.

在GIV组中，临床相关的生活质量(QoL)改善发生在治疗结束后的第15个月，这比GV/RV组晚，可能是由于治疗相关症状负担较高所致。

This trial was registered at www.clinicaltrials.gov as NCT02950051.

该试验已在www.clinicaltrials.gov上注册，注册号为NCT02950051。