Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2018 Oct 15;124(20):4044-4055. doi: 10.1002/cncr.31720. Epub 2018 Oct 11.
BACKGROUND: The outcomes of patients with relapsed or refractory (R-R) acute lymphoblastic leukemia (ALL) are poor. Inotuzumab ozogamicin and blinatumomab have single-agent activity in R-R ALL. Their addition to low-intensity chemotherapy may further improve the outcomes of patients with ALL in their first relapse. METHODS: The chemotherapy was lower in intensity than conventional hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone and was called mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (or mini-HCVD). Inotuzumab was given on day 3 of each of the first 4 cycles at 1.8 to 1.3 mg/m for cycle 1, and this was followed by 1.3 to 1.0 mg/m for subsequent cycles. From patient 39 onward, the inotuzumab dose was reduced and fractionated into weekly doses (0.6 and 0.3 mg/m during cycle 1 and 0.3 and 0.3 mg/m during subsequent cycles), and blinatumomab was administered for up to 4 cycles after inotuzumab therapy. RESULTS: Forty-eight patients with Philadelphia chromosome-negative ALL with a median age of 39 years were treated during their first relapse. Overall, 44 patients (92%) responded, with 35 of them (73%) achieving a complete response. The overall minimal residual disease negativity rate among the responders was 93%. Twenty-four patients (50%) underwent allogeneic stem cell transplantation (ASCT). Veno-occlusive disease of any grade occurred in 5 patients (10%). With a median follow-up of 31 months, the median progression-free survival (PFS) and the median overall survival (OS) were 11 and 25 months, respectively. The 2-year PFS and OS rates were 42% and 54%, respectively. Of the 24 patients (50%) who underwent ASCT, 14 patients were alive at the last follow-up (13 [54%] in remission). Of the remaining 20 responding patients who did not undergo subsequent ASCT, 6 (30%) remained in remission at the last follow-up. According to propensity score matching, the combination of mini-HCVD and inotuzumab with or without blinatumomab conferred better outcomes than intensive salvage chemotherapy or inotuzumab alone. CONCLUSIONS: The combination of inotuzumab and low-intensity mini-HCVD chemotherapy with or without blinatumomab shows encouraging results in patients with ALL in first salvage.
背景：复发或难治性（R-R）急性淋巴细胞白血病（ALL）患者的预后较差。依妥珠单抗奥佐米星和blinatumomab 在 R-R ALL 中有单药活性。它们与低强度化疗联合应用可能会进一步改善首次复发 ALL 患者的预后。
方法：化疗强度低于常规的高剂量环磷酰胺、长春新碱、阿霉素和地塞米松，称为 mini-HCVD（mini-高剂量环磷酰胺、长春新碱和地塞米松）。依妥珠单抗在第 1 至第 4 个周期的第 3 天，每个周期 1.8 至 1.3 mg/m，随后是后续周期的 1.3 至 1.0 mg/m。从第 39 例患者开始，依妥珠单抗剂量减少并分为每周剂量（第 1 周期 0.6 和 0.3 mg/m，后续周期 0.3 和 0.3 mg/m），依妥珠单抗治疗后最多给予 4 个周期的blinatumomab。
结果：48 例中位年龄为 39 岁的费城染色体阴性 ALL 患者在首次复发时接受了治疗。总体而言，44 例（92%）患者有反应，其中 35 例（73%）达到完全缓解。应答者的总微小残留病阴性率为 93%。24 例（50%）患者接受了异基因造血干细胞移植（ASCT）。5 例（10%）患者发生任何级别静脉阻塞性疾病。中位随访 31 个月时，中位无进展生存期（PFS）和中位总生存期（OS）分别为 11 个月和 25 个月。2 年 PFS 和 OS 率分别为 42%和 54%。24 例（50%）接受 ASCT 的患者中，14 例在最后一次随访时存活（缓解期 13 例[54%]）。在其余 20 例未接受后续 ASCT 的应答者中，6 例（30%）在最后一次随访时仍处于缓解期。根据倾向评分匹配，mini-HCVD 联合依妥珠单抗加或不加blinatumomab 的联合方案比强化挽救性化疗或依妥珠单抗单药治疗的疗效更好。
结论：依妥珠单抗联合低强度 mini-HCVD 化疗加或不加blinatumomab 治疗首次挽救的 ALL 患者显示出令人鼓舞的结果。
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