University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Goethe University, Frankfurt, Germany.
Leuk Res. 2020 Jan;88:106283. doi: 10.1016/j.leukres.2019.106283. Epub 2019 Nov 25.
Minimal residual disease (MRD) negativity is a key prognostic indicator of outcome in acute lymphocytic leukemia. In the INO-VATE trial (clinicaltrials.gov identifier: NCT01564784), patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab versus standard chemotherapy achieved greater remission and MRD-negativity rates as well as improved overall survival: hazard ratio 0.75, one-sided P = 0.0105. The current analysis assessed the prognostic value of MRD negativity at the end of inotuzumab treatment. All patients who received inotuzumab (n = 164) were included. Among patients with complete remission/complete remission with incomplete hematologic response (CR/CRi; n = 121), MRD-negative status (by multiparametric flow cytometry) was defined as <1 × 10 blasts/nucleated cells. MRD negativity was achieved in 76 patients at the end of treatment. Compared with MRD-positive, MRD-negative status with CR/CRi was associated with significantly improved overall survival and progression-free survival, respectively: hazard ratio (97.5% confidence interval; one-sided P-value) 0.512 (97.5% CI [0.313-0.835]; P = 0.0009) and 0.423 (97.5% CI [0.256-0.699]; P < 0.0001). Median overall survival was 14.1 versus 7.2 months, in the MRD-negative versus MRD-positive groups. Patients in first salvage who achieved MRD negativity at the end of treatment experienced significantly improved survival versus that seen in MRD-positive patients, particularly for those patients who proceeded to stem cell transplant. Among patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab, those with MRD-negative CR/CRi had the best survival outcomes.
微小残留病（MRD）阴性是急性淋巴细胞白血病预后的关键指标。在 INO-VATE 试验（clinicaltrials.gov 标识符：NCT01564784）中，接受伊妥珠单抗与标准化疗的复发/难治性急性淋巴细胞白血病患者实现了更高的缓解率和 MRD 阴性率，以及改善的总生存率：风险比 0.75，单侧 P = 0.0105。本分析评估了伊妥珠单抗治疗结束时 MRD 阴性的预后价值。所有接受伊妥珠单抗治疗的患者（n = 164）均被纳入。在完全缓解/不完全血液学缓解的患者（n = 121）中，MRD 阴性状态（通过多参数流式细胞术定义）定义为 <1 × 10 个 blast/有核细胞。164 例患者中有 76 例在治疗结束时达到 MRD 阴性。与 MRD 阳性相比，CR/CRi 时的 MRD 阴性状态与总生存率和无进展生存率分别显著相关：风险比（97.5%置信区间；单侧 P 值）0.512（97.5%CI[0.313-0.835]；P = 0.0009）和 0.423（97.5%CI[0.256-0.699]；P < 0.0001）。MRD 阴性组的中位总生存率为 14.1 个月，MRD 阳性组为 7.2 个月。在治疗结束时达到 MRD 阴性的首次挽救治疗患者的生存明显优于 MRD 阳性患者，尤其是那些进行了干细胞移植的患者。在接受伊妥珠单抗治疗的复发/难治性急性淋巴细胞白血病患者中，MRD 阴性 CR/CRi 的患者生存结局最佳。
