在首次挽救性化疗中，采用奥加米星单抗联合 mini-hyper-CVD 的化疗免疫治疗，联合或不联合blinatumomab，对费城染色体阴性急性淋巴细胞白血病患者具有高度疗效。
Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage.
机构信息
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.
出版信息
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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