The First Central Clinical College of Tianjin Medical University, Tianjin, 300380, China.
Nankai University School of Medicine, Tianjin, 300380, China.
J Transl Med. 2024 Oct 2;22(1):888. doi: 10.1186/s12967-024-05705-7.
The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10-20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy.
A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored.
Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs.
Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.
在被诊断为急性髓系白血病（AML）的患者中，大约有 10-20%患有髓外疾病（EMD）。这些患者的病因、治疗反应和预后与没有 EMD 的患者明显不同。CLL1 CAR-T 疗法在治疗难治性和复发性 AML 患者方面已显示出令人满意的疗效和安全性。然而，人们对髓外病灶对 CLL1 CAR-T 疗法疗效的潜在影响表示担忧。
本研究共纳入 47 例患者，其中 27 例为孤立性 AML 肿瘤骨髓浸润，20 例为 AML 骨髓和髓外浸润。在天津市第一中心医院血液科实验室中制造并严格控制 CLL1 CAR-T 细胞。在 CAR-T 细胞输注后评估疗效和不良反应，同时密切监测 CAR-T 细胞的扩增、细胞因子的释放等指标。
在 20 例 EMD 患者和 27 例无 EMD 患者中，骨髓完全缓解率分别为 65.00%和 81.48%。同时，在 EMD 患者中，评估 CLL1 CAR-T 细胞对髓外病灶的疗效时，55.00%的患者达到完全缓解，10.00%的患者达到部分缓解。尽管 EMD 患者的总体生存率、无进展生存率和缓解期持续时间似乎比无 EMD 患者短，但差异无统计学意义。两组并发症发生率相似。同时，有 EMD 和无 EMD 患者的 CAR-T 细胞扩增水平和伴随细胞因子释放无显著差异。
本研究结果表明，CLL1 CAR-T 疗法对 AML 伴 EMD 患者有效，且并发症发生率在可接受范围内。CLL1 CAR-T 疗法作为一种理想的 AML 患者策略，无论是否存在 EMD，都能有效改善 AML 患者的病情，为他们提供接受根治性造血干细胞移植的机会，并显著改善其预后。
