Department of Medicine III - Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Clin Cancer Res. 2024 Oct 15;30(20):4690-4700. doi: 10.1158/1078-0432.CCR-24-1798.
Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency and subtypes of SPMs following CAR-T in lymphoma and myeloma, we performed a systematic review and meta-analysis.
A literature search was conducted in the MEDLINE, Embase, and Cochrane CENTRAL databases. Following the extraction of SPM cases and assignment of malignant origin, we analyzed SPM point estimates using random effects models.
We identified 326 SPMs across 5,517 patients from 18 clinical trials and 7 real-world studies. With a median follow-up of 21.7 months, the overall SPM point estimate was 6.0% (95% confidence interval, 4.8%-7.4%). SPM estimates were associated with treatment setting (clinical trials > real-world studies), duration of follow-up, and number of prior treatment lines, which were each confirmed as independent study-level risk factors of SPM in a meta-regression model. A subgroup meta-analysis of the four trials that randomized CAR-T versus standard-of-care revealed a similar risk of SPM with either treatment strategy (P = 0.92). In a distribution analysis of SPM subtypes, hematologic malignancies were the most common entity (37%), followed by solid tumors (27%) and non-melanoma skin cancers (16%). T-cell malignancies represented a small minority of events (1.5%). We noted disease- and product-specific variations in SPM distribution.
These data raise awareness of SPM as a clinically relevant long-term adverse event in patients receiving CAR T-cell therapy. However, our findings do not indicate that SPM frequency is higher with CAR-T versus previous standard-of-care strategies.
嵌合抗原受体（CAR）T 细胞疗法是血液恶性肿瘤的一种有效免疫疗法，但患者可能会出现长期的不良反应，包括影响发病率和死亡率的第二原发性恶性肿瘤（SPM）。为了描绘淋巴瘤和骨髓瘤患者接受 CAR-T 后 SPM 的频率和亚型，我们进行了系统评价和荟萃分析。
在 MEDLINE、Embase 和 Cochrane CENTRAL 数据库中进行文献检索。在提取 SPM 病例并确定恶性起源后，我们使用随机效应模型分析 SPM 点估计。
我们从 18 项临床试验和 7 项真实世界研究中确定了 5517 名患者的 326 例 SPM。中位随访时间为 21.7 个月，总体 SPM 点估计为 6.0%（95%置信区间，4.8%-7.4%）。SPM 估计与治疗环境（临床试验>真实世界研究）、随访时间和先前治疗线的数量相关，这些因素在荟萃回归模型中被确认为 SPM 的独立研究水平危险因素。对四项将 CAR-T 与标准护理进行随机分组的试验进行的亚组荟萃分析显示，两种治疗策略的 SPM 风险相似（P=0.92）。在 SPM 亚型的分布分析中，血液系统恶性肿瘤是最常见的实体肿瘤（37%），其次是实体肿瘤（27%）和非黑色素瘤皮肤癌（16%）。T 细胞恶性肿瘤占少数（1.5%）。我们注意到 SPM 分布存在疾病和产品特异性差异。
这些数据提高了人们对接受 CAR-T 治疗的患者出现 SPM 作为一种临床相关的长期不良反应的认识。然而，我们的研究结果并未表明 CAR-T 与以前的标准治疗策略相比，SPM 的频率更高。
