Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation.

Methods

In a Phase II trial of HLA-matched or mismatched unrelated donor mobilized blood HCT (ClinicalTrials.gov identifier: NCT03246906), adults with hematologic malignancies ineligible for myeloablative HCT were randomly assigned 1:1 to GVHD prophylaxis with SIR/CSP/PTCy (50 mg/kg once daily on days +3, +4) or SIR/CSP/MMF.

在一项针对HLA相合或不相合无关供体动员血造血干细胞移植（HCT）的II期试验中（ClinicalTrials.gov注册号：NCT03246906），不适合进行清髓性HCT的成年血液恶性肿瘤患者被随机分配为1:1接受GVHD预防治疗，一组使用SIR/CSP/PTCy（第+3、+4天每天一次，50 mg/kg），另一组使用SIR/CSP/MMF。

The primary end point was 1-year chronic GVHD-free relapse-free survival (CRFS).

主要终点是1年慢性移植物抗宿主病（GVHD）无复发生存（CRFS）情况。

Results

One hundred forty-five patients were randomly assigned and transplanted.

共有145名患者被随机分配并接受了移植。

Median follow-up among survivors was 3.0 (range, 0.6-7.0) years.

幸存者中的中位随访时间为3.0年（范围，0.6-7.0年）。

Comparing PTCy-based with non-PTCy-based immunosuppression, estimated 1-year CRFS was 73% (95% CI, 61% to 82%) versus 48% (95% CI, 36% to 59%), translating into a hazard ratio(HR) for CRFS failure of 0.46 (95% CI, 0.26 to 0.79; P = .005) for PTCy.

比较基于PTCy与非基于PTCy的免疫抑制治疗，估计的1年无复发生存（CRFS）为73%（95%置信区间，61%至82%）与48%（95%置信区间，36%至59%），转化为PTCy组的无复发生存失败的风险比（HR）为0.46（95%置信区间，0.26至0.79；P = .005）。

Probabilities of acute GVHD (aGVHD) grades II-IV and III-IV, respectively, were 40% versus 42% and 6% versus 10%.

急性移植物抗宿主病（aGVHD）II-IV级和III-IV级的概率分别为40%对42%和6%对10%。

One-year estimates for secondary end points were as follows: moderate-to-severe cGVHD, 3% (95% CI, 1% to 9%) versus 33% (95% CI, 22% to 44%); relapse, 15% versus 15%; progression-free survival, 75% versus 78%; survival, 86% versus 86%; and nonrelapse mortality, 10% versus 7%.

次要终点的一年估计值如下：中度至重度慢性移植物抗宿主病（cGVHD）为3%（95%置信区间，1%至9%）对33%（95%置信区间，22%至44%）；复发为15%对15%；无进展生存期为75%对78%；总生存为86%对86%；非复发死亡率为10%对7%。

The HR of ≥grade 3 infections with PTCy versus non-PTCy was 2.65 (95% CI, 1.41 to 4.97; P = .003).

使用PTCy与非PTCy相比，≥3级感染的危险比为2.65（95% 置信区间，1.41至4.97；P = .003）。

Conclusions

After HLA-matched or mismatched unrelated donor mobilized blood HCT, replacing MMF with PTCy, when used in combination with SIR and CSP, significantly reduced risk of cGVHD, without increasing risks of aGVHD or relapse.

在HLA匹配或不匹配无关供体动员的血液造血干细胞移植后，用PTCy替代MMF，当与SIR和CSP联合使用时，显著降低了慢性移植物抗宿主病（cGVHD）的风险，而没有增加急性移植物抗宿主病（aGVHD）或复发的风险。

Thus, the combination of PTCy and SIR/CSP may have synergistic cGVHD-protective effects warranting further study.

因此，PTCy和SIR/CSP的联合使用可能具有协同的慢性移植物抗宿主病保护效果，值得进一步研究。