Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hematol Oncol. 2022 Dec;40(5):876-884. doi: 10.1002/hon.3072. Epub 2022 Sep 6.
Adult T-cell leukemia/lymphoma (ATL) patients have a very poor prognosis. The humanized anti-CCR4 therapeutic monoclonal antibody, mogamulizumab, is a key agent for ATL treatment. Our previous integrated molecular analysis demonstrated that among all the driver genes in ATL, CCR7 gene alterations were significantly associated with clinical response to mogamulizumab. Accordingly, here we investigated the detailed clinical impact of CCR7 alterations in a larger cohort of ATL patients. These CCR7 alterations, most of which lead to C-terminus truncations, were observed in 27 of 223 patients (12%). For patients receiving mogamulizumab but not allogeneic hematopoietic stem cell transplantation (HSCT), CCR7 alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab of 0.7 years for 12 patients with CCR7 alterations vs. 1.6 years for 72 patients without, p = 0.020). On the other hand, the presence or absence of CCR7 alterations had no significant impact on survival in the entire cohort (median overall survival of 1.4 and 1.8 years, respectively, p = 0.901), or on the survival of patients receiving allogeneic HSCT (median survival from the day of transplantation of 0.9 years for 6 patients with CCR7 alterations and 1.4 years for 48 without, p = 0.543). Multivariate analysis indicated that patients with CCR4 alterations but lacking CCR7 alterations (n = 20) had significantly better survival after receiving mogamulizumab-containing treatments (hazard ratio for survival, 0.437, 95% confidence interval, 0.192-0.994). This study contributes to the establishment of precision medicine for ATL.
成人 T 细胞白血病/淋巴瘤（ATL）患者的预后非常差。人源化抗 CCR4 治疗性单克隆抗体 mogamulizumab 是 ATL 治疗的关键药物。我们之前的综合分子分析表明，在 ATL 中的所有驱动基因中，CCR7 基因改变与 mogamulizumab 的临床反应显著相关。因此，在这里我们在更大的 ATL 患者队列中研究了 CCR7 改变的详细临床影响。这些 CCR7 改变，大多数导致 C 端截断，在 223 名患者中的 27 名（12%）中观察到。对于接受 mogamulizumab 但未接受异基因造血干细胞移植（HSCT）的患者，CCR7 改变与较差的生存显著相关（接受 mogamulizumab 治疗的 12 例 CCR7 改变患者的中位生存时间为 0.7 年，而 72 例无 CCR7 改变患者的中位生存时间为 1.6 年，p=0.020）。另一方面，CCR7 改变的存在与否对整个队列的生存没有显著影响（中位总生存时间分别为 1.4 年和 1.8 年，p=0.901），也对接受异基因 HSCT 的患者的生存没有影响（6 例 CCR7 改变患者的移植后中位生存时间为 0.9 年，48 例无 CCR7 改变患者的中位生存时间为 1.4 年，p=0.543）。多变量分析表明，接受 mogamulizumab 治疗的 CCR4 改变但缺乏 CCR7 改变的患者（n=20）生存显著改善（生存风险比，0.437，95%置信区间，0.192-0.994）。这项研究为 ATL 的精准医学奠定了基础。
