Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia
Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia
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DOI：
10.1182/blood-2018-10-879429
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发表时间：
2019-03-07
期刊：
影响因子：
20.3
通讯作者：
Keating, Michael J.
中科院分区：
文献类型：
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作者：
Burger, Jan A.;Sivina, Mariela;Keating, Michael J.
伊布替尼是一种口服的布鲁顿酪氨酸激酶共价抑制剂，是治疗慢性淋巴细胞白血病（CLL）的有效药物。为了确定利妥昔单抗是否能为伊布替尼提供额外的益处，我们进行了一项伊布替尼与伊布替尼加利妥昔单抗的随机单中心试验。需要治疗的CLL患者随机接受28天周期的每日一次伊鲁替尼420 mg，作为单药（n = 104）或与利妥昔单抗（375 mg/m2; n = 104）一起使用，在周期1期间每周给药一次，然后每个周期一次，直到周期6。主要终点是意向治疗人群的无进展生存期（PFS）。我们招募了208名CLL患者，181名复发性CLL患者和27名未经治疗的高危疾病患者（17 p缺失或TP 53突变）。中位随访36个月后，接受伊鲁替尼治疗的患者的Kaplan-Meier PFS估计值为86%（95%置信区间[CI]，76.6-91.9），接受伊鲁替尼+利妥昔单抗治疗的患者为86.9%（95% CI，77.3-92.6）。同样，两组的缓解率相同（总缓解率为92%）。然而，在接受伊鲁替尼加利妥昔单抗治疗的患者中，外周血淋巴细胞计数恢复正常的时间和完全缓解的时间较短，骨髓中的残留疾病水平较低。我们的结论是，在复发和初治的高危CLL患者中，利妥昔单抗加用伊鲁替尼未能改善PFS。然而，接受伊曲替尼联合利妥昔单抗治疗的患者更快地达到缓解，并实现了显著更低的残留疾病水平。鉴于这些结果，伊曲替尼作为单药治疗仍然是CLL的当前标准治疗。
Ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase, is an effective therapy for patients with chronic lymphocytic leukemia (CLL). To determine whether rituximab provides added benefit to ibrutinib, we conducted a randomized single-center trial of ibrutinib vs ibrutinib plus rituximab. Patients with CLL requiring therapy were randomized to receive 28-day cycles of once-daily ibrutinib 420 mg, either as a single agent (n = 104), or together with rituximab (375 mg/m(2); n = 104), given weekly during cycle 1, then once per cycle until cycle 6. The primary end point was progression-free survival (PFS) in the intention-to-treat population. We enrolled 208 patients with CLL, 181 with relapsed CLL and 27 treatment-naive patients with high-risk disease (17p deletion or TP53 mutation). After a median follow-up of 36 months, the Kaplan-Meier estimates of PFS were 86% (95% confidence interval [CI], 76.6-91.9) for patients receiving ibrutinib, and 86.9% (95% CI, 77.3-92.6) for patients receiving ibrutinib plus rituximab. Similarly, response rates were the same in both arms (overall response rate, 92%). However, time to normalization of peripheral blood lymphocyte counts and time to complete remission were shorter, and residual disease levels in the bone marrow were lower, in patients receiving ibrutinib plus rituximab. We conclude that the addition of rituximab to ibrutinib in relapsed and treatment-naive high-risk patients with CLL failed to show improvement in PFS. However, patients treated with ibrutinib plus rituximab reached their remissions faster and achieved significantly lower residual disease levels. Given these results, ibrutinib as single-agent therapy remains current standard-of-care treatment in CLL.