Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study
Transplantation in adults with relapsed/refractory acute lymphoblastic leukemia who are treated with blinatumomab from a phase 3 study
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DOI：
10.1002/cncr.32335
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发表时间：
2019-12-01
期刊：
影响因子：
6.2
通讯作者：
Stein, Anthony S.
中科院分区：
文献类型：
--
作者：
Jabbour, Elias J.;Goekbuget, Nicola;Stein, Anthony S.
背景Blinatumomab是一种双特异性T细胞参与（BiTE（R））免疫肿瘤学疗法，在3期TOWER研究中，在复发性/难治性B细胞前体急性淋巴细胞白血病（R/R ALL）成人患者中，上级总生存期优于标准治疗化疗（SOC）。在此，作者报告了Blinatumomab治疗后接受异基因造血干细胞移植（HSCT）的患者的临床特征和结局。方法在TOWER研究中，成人R/R ALL患者以2：1的比例随机接受Blinatumomab或SOC治疗。研究治疗包括2个周期的Blinatumomab或SOC诱导治疗，随后进行巩固和维持治疗。在第一个周期后的任何时间，符合HSCT条件的患者可以继续进行HSCT。结果在研究期间接受HSCT的97例患者中，接受Blinatumomab治疗的患者（65例患者）和接受SOC治疗的患者（32例患者）的基线特征基本相当，供体类型相似。无证据表明Blinatumomab治疗患者与SOC治疗患者之间HSCT的生存获益存在差异（P = .68）。根据描述性统计量，在Blinatumomab治疗后达到完全缓解且血液学完全、部分或不完全恢复的患者中，未观察到HSCT与未接受HSCT相比的生存获益（比值比，1.17; 95% CI，0.54-2.53）。在既往未接受过挽救治疗且对Blinatumomab有极轻微残留疾病应答的患者中，无论研究期间HSCT状态如何，均获得了最佳结局。结论生存率受研究治疗反应和挽救状态的影响，与研究中HSCT状态无关。应谨慎解读这些数据，因为本研究并非旨在前瞻性评估Blinatumomab治疗后HSCT相关的生存结局。总结本研究前的证据：在复发性/难治性前体B细胞急性淋巴细胞白血病成人患者中，与标准治疗化疗相比，Blinatumomab具有上级形态学和分子学缓解率以及上级总体结局。本研究的附加价值：在首次挽救治疗中达到微小残留疾病缓解的患者中观察到了blinatumomab的最佳结局，无论后续是否进行了异基因干细胞移植（HSCT）。
Background Blinatumomab, a bispecific T-cell-engaging (BiTE (R)) immuno-oncology therapy, demonstrated superior overall survival versus standard-of-care chemotherapy (SOC) in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R ALL) in the phase 3 TOWER study. Herein, the authors reported clinical features and outcomes for those patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with blinatumomab. Methods In the TOWER study, adults with R/R ALL were randomized 2:1 to receive blinatumomab or SOC. Study treatment consisted of 2 cycles of induction with blinatumomab or SOC followed by consolidation and maintenance therapy. At any time after the first cycle, patients who were eligible for HSCT could proceed to HSCT. Results Of the 97 patients who underwent HSCT during the study, baseline characteristics generally were comparable and donor types were similar between the patients treated with blinatumomab (65 patients) and those receiving SOC (32 patients). There was no evidence to suggest that the survival benefit of HSCT differed between the patients treated with blinatumomab and those receiving SOC (P = .68). On the basis of descriptive statistics, a survival benefit of HSCT versus no HSCT was not observed in patients who achieved complete remission with full, partial, or incomplete hematologic recovery with blinatumomab (odds ratio, 1.17; 95% CI, 0.54-2.53). The best outcomes were achieved in patients with no prior salvage therapy and with minimal residual disease response to blinatumomab regardless of on-study HSCT status. Conclusions Survival was found to be driven by response to study treatment and by salvage status regardless of on-study HSCT status. These data should be interpreted with caution because the current study was not designed to prospectively assess survival outcomes associated with HSCT after blinatumomab. Lay SummaryEvidence before this study: Blinatumomab is associated with superior morphologic and molecular response rates and superior overall outcome when compared with standard of care chemotherapy in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Added value of this study: The best outcomes with blinatumomab were observed in patients who achieved minimal residual disease remission in first salvage treatment regardless of subsequent allogeneic stem cell transplantation (HSCT).