放疗与嵌合抗原受体 T 细胞（CAR T 细胞）疗法的协同作用——放疗在 CAR T 细胞疗法联合治疗中作用的多中心分析。
Potential synergy between radiotherapy and CAR T-cells - a multicentric analysis of the role of radiotherapy in the combination of CAR T cell therapy.
机构信息
Department of Radiation Oncology and Cyberknife Center, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Institute of Medical Statistics and Computational Biology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
出版信息
Radiother Oncol. 2023 Jun;183:109580. doi: 10.1016/j.radonc.2023.109580. Epub 2023 Feb 25.
BACKGROUND
Chimeric antigen receptor (CAR) T-cell therapy has improved the limited overall survival (OS) of patients with intensively pretreated diffuse large B-cell lymphoma (DLBCL). However, the potentially life-threatening toxicities of CAR T-cells and early relapses remain a challenge. As suggested by smaller monocentric analyses, radiotherapy (RT) in combination with CAR T-cells may have an immunomodulatory effect.
METHOD/ RESULTS: In this multicentric retrospective analysis, we investigated potentially synergistic effects of RT and CAR T-cells. Of 78 patients from four centers who received CAR T-cell therapy for DLBCL, 37 patients underwent bridging RT or received salvage RT. RTs (median 36 gray) were well tolerated. Therapy response and disease control of CAR T-cell therapy were comparable after bridging RT or bridging systemic therapy. High-grade neurotoxicity tended to occur less frequently after bridging RT. After further disease progression, patients with localized relapses showed better outcomes, compared to those in advanced stage. In the subgroup with localized relapse, patients receiving salvage RT had an increased OS, vs. those without salvage RT (1-year OS rate 89% vs. 38%, p = 0.03).
CONCLUSION
Our analysis demonstrated that RT in combination with CAR T-cells led neither to high-grade toxicities, nor to a decreased response rate. We observed better outcomes of salvage therapies in patients with localized relapses vs. those with advanced stage relapses. Especially the patients who received salvage RTs for localized relapses seem to benefit more. Further analyses are necessary to clarify whether specific synergistic effects exist, such as an enhanced anti-tumor effect of CAR T-cells from RT sensitizing.
背景
嵌合抗原受体（CAR）T 细胞疗法改善了经过强化预处理的弥漫性大 B 细胞淋巴瘤（DLBCL）患者有限的总生存期（OS）。然而，CAR T 细胞的潜在危及生命的毒性和早期复发仍然是一个挑战。较小的单中心分析表明，放射治疗（RT）与 CAR T 细胞联合可能具有免疫调节作用。
方法/结果：在这项多中心回顾性分析中，我们研究了 RT 和 CAR T 细胞联合的潜在协同作用。在来自四个中心的 78 名接受 CAR T 细胞治疗 DLBCL 的患者中，有 37 名患者接受了桥接 RT 或挽救性 RT。RT（中位数 36 格雷）耐受性良好。桥接 RT 或桥接系统性治疗后，CAR T 细胞治疗的反应和疾病控制相当。桥接 RT 后，高级别神经毒性的发生率趋于降低。进一步疾病进展后，与晚期患者相比，局部复发患者的预后更好。在局部复发的亚组中，接受挽救性 RT 的患者的 OS 增加，与未接受挽救性 RT 的患者相比（1 年 OS 率为 89%比 38%，p=0.03）。
结论
我们的分析表明，RT 与 CAR T 细胞联合既不会导致高等级毒性，也不会降低反应率。我们观察到局部复发患者的挽救治疗结局更好，与晚期复发患者相比。特别是接受局部复发挽救性 RT 的患者似乎受益更多。需要进一步分析以明确是否存在特定的协同作用，例如 RT 增敏导致 CAR T 细胞的抗肿瘤作用增强。
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