HLA 多样性与慢性骨髓性白血病的治疗反应和免治疗缓解有关

如需购买请加微信：zhikang161218，备用微信：zhikang1218

HLA 多样性与慢性骨髓性白血病的治疗反应和免治疗缓解有关

Title: HLA DIVERSITY IS ASSOCIATED WITH TREATMENT RESPONSE AND TREATMENT-FREE REMISSION IN CHRONIC MYELOID LEUKEMIA

标题： HLA 多样性与慢性髓系白血病的治疗反应和免治疗缓解有关

Type: Poster Presentation

类型： 海报展示

Session title: Chronic myeloid leukemia - Clinical

分会标题：慢性髓系白血病--临床

Background: 

Achieving a deep molecular response and a subsequent treatment-free remission (TFR) are currently the two main therapeutic goals for patients with chronic-phase chronic myeloid leukemia (CP-CML). Several studies suggest that anti-tumor immunity plays an important role in the response to tyrosine kinase inhibitor (TKI) therapy. However, the impact of specific immune-related factors, particularly Human Leukocyte Antigen (HLA) polymorphisms, remains unclear.

实现深度分子反应和随后的无治疗缓解（TFR）是目前慢性期慢性髓系白血病（CP-CML）患者的两个主要治疗目标。多项研究表明，抗肿瘤免疫在酪氨酸激酶抑制剂（TKI）治疗反应中发挥着重要作用。然而，特定免疫相关因素，尤其是人类白细胞抗原（HLA）多态性的影响仍不清楚。

Aims: 

This retrospective bi-centric study investigates the relationship between HLA diversity and both response to TKI therapy and TFR in patients with CP-CML.

这项回顾性双中心研究调查了 CP-CML 患者的 HLA 多样性与 TKI 治疗反应和 TFR 之间的关系。

Methods:

High-resolution molecular HLA typing data from CP-CML patients at diagnosis were collected. Individual HLA polymorphisms were extracted, and the HLA Evolutionary Divergence (HED) score was calculated for both class I and class II alleles. The primary endpoints were time to deep molecular response (MR4) and TFR.

研究收集了 CP-CML 患者诊断时的高分辨率分子 HLA 分型数据。提取了单个 HLA 多态性，并计算了 I 类和 II 类等位基因的 HLA 进化分歧（HED）得分。主要终点是深度分子反应（MR4）时间和 TFR。

Results:

Between January 2002 and January 2023, 367 patients with molecularly confirmed CML and available HLA typing were identified. Of these, 286 patients with CP-CML had an available clinical follow-up.

从 2002 年 1 月到 2023 年 1 月，共发现了 367 例经分子确诊的 CML 患者，并进行了 HLA 分型。其中，286 名 CP-CML 患者接受了临床随访。

No individual HLA allele or HED score were significantly associated with time to MR4. In subgroup analysis, DQB106:04 and DRB113:02 alleles in patients treated with IMATINIB (IMA, n=106) and B44:02 allele in those treated with DASATINIB (DAS, n=50) were found to be associated with time to MR4, with no significant association found in patients treated with NILOTINIB (NIL, n=73). Multivariate analysis confirmed that the presence of at least one of these three favorable HLA alleles was significantly associated with time to MR4 in the IMA (adjusted HR [aHR] [95% CI] 3.01 [1.49-6.09], p=0.002) and DAS groups (aHR 5.92 [2.64-13.25], p<0.001), independently of gender

没有任何一个 HLA 等位基因或 HED 评分与 MR4 的时间显著相关。在亚组分析中发现，接受 IMATINIB（IMA，n=106）治疗的患者中的 DQB106:04 和 DRB113:02 等位基因以及接受 DASATINIB（DAS，n=50）治疗的患者中的 B44:02 等位基因与 MR4 发生时间有关，而接受 NILOTINIB（NIL，n=73）治疗的患者中的 DQB106:04 和 DRB113:02 等位基因与 MR4 发生时间无明显关系。多变量分析证实，在 IMA 组（调整后 HR [aHR] [95% CI] 3.01 [1.49-6.09]，p=0.002）和 DAS 组（aHR 5.92 [2.64-13.25]，p<0.001）中，这三种有利的 HLA 等位基因中至少一种的存在与 MR4 时间显著相关，与性别无关。

Among the 105 patients who attempted treatment cessation (TFR), HLA-A26:01 and A32:01 alleles were associated with an increased risk of molecular relapse. Only A32:01 and B18:01 alleles in patients treated with IMA (n=43) were identified as unfavorable in subgroup analysis. Multivariate analysis revealed a higher probability of molecular relapse for the high-risk HLA alleles in patients from the overall cohort (adjusted HR (aHR) [95%CI] 3.60 [1.94-6.65], p<0.001) and in the IMA group (aHR 6.88 [2.57-18.45], p<0.001), independently of MR4 duration before TKI discontinuation. Conversely, a high HED diversity score for HLA-C was associated with sustained TFR in DAS-treated patients before TKI discontinuation (aHR 0.23 [0.06-0.86], p=0.03).

在 105 名尝试停止治疗（TFR）的患者中，HLA-A26:01 和 A32:01 等位基因与分子复发风险增加有关。在亚组分析中，只有接受 IMA 治疗的患者（43 人）中的 A32:01 和 B18:01 等位基因被确定为不利因素。多变量分析显示，高风险 HLA 等位基因患者在总体队列（调整 HR (aHR) [95%CI] 3.60 [1.94-6.65]，p<0.001）和 IMA 组（aHR 6.88 [2.57-18.45]，p<0.001）中的分子复发概率较高，与停用 TKI 前的 MR4 持续时间无关。相反，在停用 TKI 之前，HLA-C 的高 HED 多样性评分与 DAS 治疗患者的持续 TFR 相关（aHR 0.23 [0.06-0.86]，p=0.03）。

Summary/Conclusion: 

These preliminary results suggest that specific HLA alleles may influence TKI response and molecular relapse risk after treatment discontinuation. The finding that HLA-C diversity as assessed by the HED score was associated with TFR maintenance only in the DAS group suggests that distinct immune mechanisms may be involved in sustaining remission depending on the TKI used. These results warrant further validation in larger multicenter studies.

这些初步结果表明，特定的 HLA 等位基因可能会影响 TKI 反应和治疗终止后的分子复发风险。通过 HED 评分评估的 HLA-C 多样性仅与 DAS 组的 TFR 维持有关，这一发现表明，根据所使用的 TKI，不同的免疫机制可能参与维持缓解。这些结果需要在更大规模的多中心研究中进一步验证。