Analysis Group, Inc., Los Angeles, CA, USA.
Amgen Inc., Thousand Oaks, CA, USA.
Adv Ther. 2019 Apr;36(4):950-961. doi: 10.1007/s12325-019-0873-7. Epub 2019 Feb 13.
In the absence of head-to-head trials, this analysis aimed to provide a fair indirect comparison of the efficacy between blinatumomab and inotuzumab ozogamicin (InO), two treatments for adult patients with relapsed or refractory acute lymphoblastic leukemia (R/R ALL) who received no more than one prior salvage therapy, by adjusting for cross-trial differences.
Patient-level data from the Phase 3 blinatumomab trial TOWER and published aggregated data from the Phase 3 InO trial INO-VATE-ALL were used to conduct matching-adjusted indirect comparisons. Patients with 2+ prior salvage therapies from TOWER were excluded because such patients were not included in INO-VATE-ALL. To ensure balance in the remaining patients, baseline characteristics for the TOWER patients were weighted to match the average baseline characteristics in INO-VATE-ALL, including sex, age, race, performance status, bone marrow blast, previous salvage therapy, previous allogeneic transplantation, complete remission with complete hematologic recovery (CR) to most recent induction therapy, and duration of first remission. Overall survival (OS), including median and restricted mean survival time (RMST) at 12 and 20.7 months, and CR were estimated and compared.
A total of 310 patients in TOWER were included (blinatumomab, n = 203; standard of care chemotherapy, n = 107). After matching the listed baseline characteristics, the median OS was 9.3 months for blinatumomab and 7.7 months for InO (weighted log-rank test p = 0.4). The relative RMST at 12 months was 1.6 months longer for blinatumomab than for InO [95% CI (0.1, 3.2); p = 0.04]; at 20.7 months the RMST was not significantly different. The CR rates were similar [anchor-based difference = - 2.8%, 95% CI (- 17.5%, 11.9%); p = 0.71].
After adjusting for cross-trial differences, blinatumomab demonstrated a similar CR rate and potential OS benefit versus InO among adult patients with R/R ALL who received no more than one prior salvage therapy. Further studies are suggested to confirm this finding.
Amgen.
由于缺乏头对头试验，本分析旨在通过调整交叉试验差异，为接受不超过一次既往挽救治疗的复发/难治性急性淋巴细胞白血病（R/R ALL）成年患者的blinatumomab 和 inotuzumab ozogamicin（InO）两种治疗方法的疗效提供公平的间接比较。
使用来自 3 期blinatumomab 试验 TOWER 的患者水平数据和来自 3 期 InO 试验 INO-VATE-ALL 的已发表汇总数据进行匹配调整间接比较。从 TOWER 中排除了接受 2+ 次既往挽救治疗的患者，因为这些患者未被纳入 INO-VATE-ALL。为了确保剩余患者的平衡，对 TOWER 患者的基线特征进行加权，以匹配 INO-VATE-ALL 中的平均基线特征，包括性别、年龄、种族、表现状态、骨髓原始细胞、既往挽救治疗、既往同种异体移植、与最近诱导治疗相关的完全缓解（CR）至完全血液学恢复（CR）和首次缓解的持续时间。估计并比较了总生存期（OS），包括 12 个月和 20.7 个月的中位和限制平均生存时间（RMST）以及 CR。
TOWER 中共有 310 例患者入组（blinatumomab，n=203；标准治疗化疗，n=107）。在匹配列出的基线特征后，blinatumomab 的中位 OS 为 9.3 个月，InO 为 7.7 个月（加权对数秩检验 p=0.4）。blinatumomab 治疗 12 个月的相对 RMST 长 1.6 个月[95%CI（0.1，3.2）；p=0.04]；在 20.7 个月时，RMST 无显著差异。CR 率相似[基于锚点的差异=-2.8%，95%CI（-17.5%，11.9%）；p=0.71]。
在调整交叉试验差异后，blinatumomab 与接受不超过一次既往挽救治疗的 R/R ALL 成年患者的 InO 相比，显示出相似的 CR 率和潜在的 OS 获益。建议进一步研究以证实这一发现。
安进。
