Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Section of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
J Immunother Cancer. 2021 Feb;9(2). doi: 10.1136/jitc-2020-001818.
Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.
A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.
Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2-4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).
ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.
免疫检查点抑制剂（ICIs）在异基因造血干细胞移植（alloHCT）后被用于逆转免疫功能障碍。然而，ICIs 在 alloHCT 后使用的一个主要关注点是移植物抗宿主病（GVHD）的风险增加。我们分析了接受 alloHCT 后接受 ICI 治疗的患者中 GVHD 预防与 GVHD 发生率之间的关系。
对 21 例接受抗程序性细胞死亡蛋白 1（16 例）或抗细胞毒性 T 淋巴细胞相关抗原 4（5 例）治疗的急性髓系白血病（n=16）或骨髓增生异常综合征（n=5）患者进行回顾性研究，这些患者在 alloHCT 后因疾病复发而接受治疗。分析了 GVHD 预防类型与 GVHD 发生率之间的关系。
4 例（19%）发生急性 GVHD。急性 GVHD 的发生率仅与移植后 GVHD 预防类型有关；包括干细胞来源、供体类型、alloHCT 时年龄、预处理方案和既往 GVHD 史在内的其他变量均与急性 GVHD 的频率无关。12 例患者接受移植后环磷酰胺（PTCy）预防 GVHD。与未接受 PTCy 的患者相比，接受 PTCy 的患者 alloHCT 后开始 ICI 治疗的中位时间明显缩短（中位时间 5.1 个月与 26.6 个月）。尽管早期开始 ICI 治疗，但接受 PTCy 的患者 2-4 级急性 GVHD 的累积发生率明显低于未接受 PTCy 的患者（16%与 22%；p=0.7）。在控制合并症和 alloHCT 至 ICI 治疗开始的时间后，分析表明 PTCy 与急性 GVHD 的风险降低 90%相关（HR 0.1，95%CI 0.02 至 0.6，p=0.01）。
alloHCT 后复发的急性髓系白血病/骨髓增生异常综合征接受 ICI 治疗可能是一种安全且可行的选择。在本队列患者中，PTCy 似乎可降低急性 GVHD 的发生率。
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