Center for Cell and Gene Therapy, Baylor College of Medicine-Texas Children's Hospital, Houston, TX.
Department of Medicine, Houston Methodist Hospital, Houston, TX.
Blood. 2022 Jul 7;140(1):16-24. doi: 10.1182/blood.2022015728.
Subsequent malignancies are well-documented complications in long-term follow-up of cancer patients. Recently, genetically modified immune effector (IE) cells have shown benefit in hematologic malignancies and are being evaluated in clinical trials for solid tumors. Although the short-term complications of IE cells are well described, there is limited literature summarizing long-term follow-up, including subsequent malignancies. We retrospectively reviewed data from 340 patients treated across 27 investigator-initiated pediatric and adult clinical trials at our center. All patients received IE cells genetically modified with γ-retroviral vectors to treat relapsed and/or refractory hematologic or solid malignancies. In a cumulative 1027 years of long-term follow-up, 13 patients (3.8%) developed another cancer with a total of 16 events (4 hematologic malignancies and 12 solid tumors). The 5-year cumulative incidence of a first subsequent malignancy in the recipients of genetically modified IE cells was 3.6% (95% confidence interval, 1.8% to 6.4%). For 11 of the 16 subsequent tumors, biopsies were available, and no sample was transgene positive by polymerase chain reaction. Replication-competent retrovirus testing of peripheral blood mononuclear cells was negative in the 13 patients with subsequent malignancies tested. Rates of subsequent malignancy were low and comparable to standard chemotherapy. These results suggest that the administration of IE cells genetically modified with γ retroviral vectors does not increase the risk for subsequent malignancy.
随后发生的恶性肿瘤是癌症患者长期随访中记录良好的并发症。最近，经过基因改造的免疫效应（IE）细胞已在血液恶性肿瘤中显示出益处，并正在临床试验中评估其在实体瘤中的应用。虽然 IE 细胞的短期并发症已有详细描述，但关于长期随访的文献有限，包括随后发生的恶性肿瘤。我们回顾性分析了在我们中心进行的 27 项由研究人员发起的儿科和成人临床试验中 340 例患者的数据。所有患者均接受了经过γ逆转录病毒载体基因改造的 IE 细胞治疗复发和/或难治性血液或实体恶性肿瘤。在长达 1027 年的累计长期随访中，13 名患者（3.8%）发生了另一种癌症，共发生了 16 次事件（4 次血液恶性肿瘤和 12 次实体肿瘤）。接受基因修饰的 IE 细胞治疗的患者中，首次发生随后恶性肿瘤的 5 年累积发生率为 3.6%（95%置信区间，1.8%至 6.4%）。在 16 个随后的肿瘤中，有 11 个进行了活检，聚合酶链反应未检测到任何样本的转基因阳性。在接受后续恶性肿瘤检测的 13 名患者中，外周血单个核细胞的复制型逆转录病毒检测均为阴性。随后发生恶性肿瘤的比率较低，与标准化疗相当。这些结果表明，经γ逆转录病毒载体基因改造的 IE 细胞的给药不会增加随后发生恶性肿瘤的风险。
