Acıbadem Altunizade Hospital, Hematology Unit, İstanbul, Turkey
Acıbadem Labcell Cellular Therapy Center, İstanbul, Turkey
Turk J Haematol. 2022 Aug 25;39(3):206-210. doi: 10.4274/tjh.galenos.2022.2022.0193. Epub 2022 Jul 18.
Chimeric antigen receptor T (CAR-T) cell therapies have already made an impact on the treatment of B-cell malignancies. Although CAR-T cell therapies are promising, there are concerns about commercial products regarding their affordability and sustainability. In this preliminary study, the results of the first production and clinical data of an academic CAR-T cell (ISIKOK-19) trial in Turkey are presented.
A pilot clinical trial (NCT04206943) designed to assess the safety and feasibility of ISIKOK-19 T-cell therapy for patients with relapsed and refractory CD19+ tumors was conducted and participating patients received ISIKOK-19 infusions between October 2019 and July 2021. The production data of the first 8 patients and the clinical outcome of 7 patients who received ISIKOK-19 cell infusions are presented in this study.
Nine patients were enrolled in the trial [5 with acute lymphoblastic leukemia (ALL) and 4 with non-Hodgkin lymphoma (NHL)], but only 7 patients could receive treatment. Two of the 3 participating ALL patients and 3 of the 4 NHL patients had complete/partial response (overall response rate: 72%). Four patients (57%) had CAR-T-related toxicities (cytokine release syndrome, CAR-T-related encephalopathy syndrome, and pancytopenia). Two patients were unresponsive and had progressive disease following CAR-T therapy. Two patients with partial response had progressive disease during follow-up.
Production efficacy and fulfillment of the criteria of quality control were satisfactory for academic production. Response rates and toxicity profiles were also acceptable for this heavily pretreated/refractory patient group. ISIKOK-19 cells appear to be a safe, economical, and efficient treatment option for CD19+ tumors. However, the findings of this study need to be supported by the currently ongoing ISIKOK-19 clinical trial.
嵌合抗原受体 T（CAR-T）细胞疗法已经对 B 细胞恶性肿瘤的治疗产生了影响。尽管 CAR-T 细胞疗法很有前途，但人们对商业产品的可负担性和可持续性表示担忧。在这项初步研究中，介绍了土耳其首例学术性 CAR-T 细胞（ISIKOK-19）试验的生产结果和临床数据。
进行了一项旨在评估 ISIKOK-19 T 细胞疗法治疗复发/难治性 CD19+肿瘤患者的安全性和可行性的Ⅰ期临床试验（NCT04206943），并于 2019 年 10 月至 2021 年 7 月期间为入组患者输注 ISIKOK-19。本研究报告了前 8 例患者的生产数据和 7 例接受 ISIKOK-19 细胞输注患者的临床结果。
该试验共纳入 9 例患者（5 例急性淋巴细胞白血病[ALL]和 4 例非霍奇金淋巴瘤[NHL]），但仅有 7 例患者可接受治疗。3 例 ALL 患者中的 2 例和 4 例 NHL 患者中的 3 例患者获得完全/部分缓解（总缓解率：72%）。4 例患者（57%）出现 CAR-T 相关毒性（细胞因子释放综合征、CAR-T 相关脑病综合征和全血细胞减少症）。2 例患者在 CAR-T 治疗后无反应且病情进展。2 例部分缓解的患者在随访期间疾病进展。
学术生产的生产效率和质量控制标准的满足令人满意。对于这一预处理/难治性患者群体，反应率和毒性谱也是可以接受的。ISIKOK-19 细胞似乎是 CD19+肿瘤的一种安全、经济且有效的治疗选择。然而，本研究的结果需要得到目前正在进行的 ISIKOK-19 临床试验的支持。
