Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Radiology, Molecular Imaging, and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Transplant Cell Ther. 2023 Apr;29(4):259.e1-259.e10. doi: 10.1016/j.jtct.2022.12.021. Epub 2022 Dec 30.
Greater tumor burden before CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy predicts lower complete response rate and shorter overall survival (OS) in patients with aggressive non-Hodgkin lymphoma (NHL). Recent patterns of failure studies have identified lesion characteristics, including size, standard uptake value (SUV), and extranodal location, as associated with post-CAR-T therapy failure. Here we analyzed the effect of bridging radiation-containing treatment (BRT) on pre-CAR-T therapy lesion- and patient-level characteristics and post-CAR-T therapy outcomes, including patterns of failure. Consecutive NHL patients who received radiation therapy from 30 days before leukapheresis until CAR T cell infusion were reviewed. Metabolic tumor volume (MTV) was contoured with a threshold SUV of 4. The first post-CAR-T therapy failures were categorized as preexisting/new/mixed with respect to pre-CAR-T therapy disease and in-field/marginal/distant with respect to BRT. Forty-one patients with diffuse large B cell lymphoma (DLBCL; n = 33), mantle cell lymphoma (n = 7), or Burkitt lymphoma (n = 1) were identified. BRT significantly improved established high-risk parameters of post-CAR-T therapy progression, including in-field median MTV (45.5 cc to .2 cc; P < .001), maximum SUV (18.1 to 4.4; P < .001), diameter (5.5 cm to 3.2 cm; P < .001), and lactate dehydrogenase (LDH; 312 to 232; P = .025). DLBCL patients with lower LDH levels post-BRT had improved progression-free survival (PFS; P = .001). In DLBCL, first failures were new in 7 of 19 patients, preexisting in 5 of 19, and mixed in 7 of 19; with respect to BRT, 4 of 19 were in-field and 4 of 19 were marginal. Post-CAR-T therapy survival was similar in patients with initially low MTV and those with newly low MTV post-BRT using a statistically determined threshold of 16 cc (PFS, 26 months versus 31 months; OS unreached for both). BRT produced significant cytoreductions in diameter, SUV, MTV, and LDH, all predictors of poor post-CAR-T therapy outcomes. Similar PFS and OS in patients with initially low MTV and those who achieved newly low MTV after BRT suggest that BRT may "convert" poor-risk patients to better risk. In the future, the response to BRT may allow for risk stratification and individualization of bridging strategies.
在接受 CD19 靶向嵌合抗原受体 T 细胞（CAR-T）治疗之前，肿瘤负荷越大，侵袭性非霍奇金淋巴瘤（NHL）患者的完全缓解率越低，总生存期（OS）越短。最近的失败模式研究已经确定了病变特征，包括大小、标准摄取值（SUV）和结外位置，与 CAR-T 治疗后失败有关。在这里，我们分析了桥接放疗（BRT）对 CAR-T 治疗前病变和患者水平特征以及 CAR-T 治疗后结局（包括失败模式）的影响。对从白细胞分离前 30 天至 CAR-T 细胞输注期间接受放疗的连续 NHL 患者进行了回顾性分析。代谢肿瘤体积（MTV）用阈值 SUV 为 4 进行描绘。CAR-T 治疗后首次失败按 CAR-T 治疗前疾病分为原有/新发/混合，并按 BRT 分为累及野/边缘/远处。确定了弥漫性大 B 细胞淋巴瘤（DLBCL；n=33）、套细胞淋巴瘤（n=7）或伯基特淋巴瘤（n=1）患者 41 例。BRT 显著改善了 CAR-T 治疗后进展的既定高危参数，包括累及野中位数 MTV（45.5 cc 至 0.2 cc；P<.001）、最大 SUV（18.1 至 4.4；P<.001）、直径（5.5 cm 至 3.2 cm；P<.001）和乳酸脱氢酶（LDH；312 至 232；P=.025）。BRT 后 LDH 水平较低的 DLBCL 患者无进展生存期（PFS；P=.001）改善。在 DLBCL 中，19 例患者中有 7 例为新发，19 例患者中有 5 例为原有，19 例患者中有 7 例为混合；关于 BRT，19 例患者中有 4 例为累及野，19 例患者中有 4 例为边缘。用统计学确定的 16 cc 阈值比较，CAR-T 治疗后使用 BRT 的患者初始 MTV 较低者和新 MTV 较低者的生存情况相似（PFS，26 个月与 31 个月；两者 OS 均未达到）。BRT 在直径、SUV、MTV 和 LDH 方面均产生了显著的细胞减少，这些都是 CAR-T 治疗后预后不良的预测因素。BRT 后初始 MTV 较低的患者和新 MTV 较低的患者的 PFS 和 OS 相似，提示 BRT 可能“转化”为高危患者为低危。未来，对 BRT 的反应可能允许对桥接策略进行风险分层和个体化。
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