Orca-T vs allogeneic hematopoietic stem cell transplantation (Precision-T): a multicenter, randomized phase 3 trial.

Early phase studies suggested improved outcomes with Orca-T, an allogeneic T-cell immunotherapy that uses purified donor regulatory T cells to prevent GVHD with significantly less immunosuppression.

早期研究显示，Orca-T这种异基因T细胞免疫疗法通过使用纯化的供体调节性T细胞预防GVHD，并显著减少了免疫抑制，改善了治疗结果。

This phase 3 trial randomized adult patients (N = 187) with acute leukemias or myelodysplastic syndrome undergoing myeloablative conditioning to receive either Orca-T with tacrolimus or a conventional allograft with tacrolimus and methotrexate (Tac/MTX), using granulocyte colony-stimulating factor-mobilized peripheral blood from HLA-matched donors.

这项III期临床试验随机分配了187名成年患者，这些患者患有急性白血病或骨髓增生异常综合征，并接受骨髓消融性预处理，以接受Orca-T联合他克莫司治疗，或接受传统的同种异体移植治疗，后者使用他克莫司和甲氨蝶呤（Tac/MTX），供体为HLA匹配的供体，使用粒细胞集落刺激因子动员的外周血。

The primary end point was survival free from moderate-to-severe chronic GVHD (cGVHD; cGFS).

主要终点是无中度至重度慢性移植物抗宿主病（cGVHD；cGFS）的生存期。

Using a stratified log-rank test, cGFS was significantly higher in the Orca-T arm than in Tac/MTX (hazard ratio, 0.26; 95% confidence interval, 0.14-0.47; P< .001).

使用分层的对数秩检验，Orca-T组的cGFS显著高于Tac/MTX组（风险比，0.26；95%置信区间，0.14-0.47；P< .001）。

One-year estimates were as follows: cGFS was 78.0% with Orca-T vs 38.4% with Tac/MTX; cumulative incidenceof moderate-to-severe cGVHD was 12.6% with Orca-T and 44.0% with Tac/MTX (Gray test P< .001); overall survivalwas 93.9% with Orca-T vs 83.1% with Tac/MTX (P = .12); GVHD-free and relapse-free survival was 63.1% and 30.9% in the Orca-T and Tac/MTX arms (P< .001), respectively; nonrelapse mortality (NRM) was 3.4% with Orca-T vs 13.2% with Tac/MTX (P = .03).

一年的估计结果如下：Orca-T组的cGFS为78.0%，而Tac/MTX组为38.4%；中度至重度cGVHD的累积发生率为Orca-T组的12.6%和Tac/MTX组的44.0%（Gray检验P< .001）；总生存率为Orca-T组的93.9%，Tac/MTX组的83.1%（P = .12）；无GVHD和无复发生存率为Orca-T组的63.1%，Tac/MTX组的30.9%（P< .001）；非复发死亡（NRM）为Orca-T组的3.4%，Tac/MTX组的13.2%（P = .03）。

Orca-T met the primary end point of improved survival free from cGVHD compared with Tac/MTX prophylaxis and should be considered a new therapeutic option with low toxicity for GVHD prophylaxis.

Orca-T 达到了改善无慢性移植物抗宿主病（cGVHD）生存期的主要终点，与 Tac/MTX 预防治疗相比，应被视为一种低毒性的GVHD预防新治疗选择。

Moreover, significantly less toxicity was observed with Orca-T patients, including fewer serious infectious complications and less NRM.

此外，与Orca-T患者相比，观察到显著较少的毒性，包括较少的严重感染并发症和较低的非复发死亡率（NRM）。

This trial was registered at www.clinicaltrials.gov as NCT05316701.

该试验已在www.clinicaltrials.gov上注册，注册号为NCT05316701。