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半定量PET参数改善CAR-T治疗淋巴瘤1个月和3个月后的预后:一项前瞻性单中心研究

Semiquantitative PET Parameters Refine Prognosis in CAR T-Treated Lymphoma After 1 and 3 Months: A Prospective Single-Center Study.

作者信息

Farolfi Andrea, Casadei Beatrice, Malizia Claudio, Ussia Riccardo, Rocchi Veronica, Paccagnella Andrea, Gentilini Marianna, Nanni Cristina, Argnani Lisa, Zinzani Pier Luigi, Fanti Stefano

机构信息

Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy;

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seragnoli", Bologna, Italy.

出版信息

J Nucl Med. 2025 Apr 17. doi: 10.2967/jnumed.125.269670.


DOI:10.2967/jnumed.125.269670
PMID:40246539
Abstract

Chimeric antigen receptor T-cell (CAR T) therapy has shown remarkable efficacy in treating relapsed or refractory large B-cell lymphoma. However, for nearly half of these patients, the therapy eventually does not achieve durable remission. We investigated whether semiquantitative PET parameters (namely, SUV, metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) could improve risk stratification 1 mo (PET1m) and 3 mo (PET3m) after CAR T infusion. In this prospective, single-center cohort study, patients with large B-cell lymphoma received axicabtagene ciloleucel or tisagenlecleucel. [F]FDG PET/CT scans were acquired at baseline, 1 mo, and 3 mo after infusion. MTV and TLG were calculated using a threshold SUV of 4 or greater. Patients were followed for overall survival (OS), progression-free survival (PFS), and duration of response (DoR). The imaging assessment was based on the Lugano recommendation for response assessment. Prognostic factors were identified using univariate and multivariate Cox regression. Sixty-one patients were enrolled, with a median follow-up of 18 mo. Twenty-eight (46%) patients died. Kaplan-Meier analysis with log-rank tests indicated a significant association of elevated Deauville score (DS), SUV, MTV, and TLG with OS (all < 0.05). DS cutoff was arbitrarily fixed at 4. The optimal SUV, MTV, and TLG cutoffs at PET1m were 9.1, 60.8, and 97.0, respectively; whereas at PET3m, they were 6.3, 120.1, and 436.9, respectively. Patients with an SUV of 6.3 or greater at PET3m had an 8-fold increase in risk of death (hazard ratio [HR], 8.15; 95% CI, 2.81-23.6; < 0.01) compared with those below this cutoff. Similarly, higher MTV (≥120.1) at PET3m yielded a nearly 10-fold risk (HR, 9.87; 95% CI, 3.65-26.7; < 0.01). DS, SUV, MTV, and TLG at both PET1m and PET3m were associated with OS and PFS (all < 0.05), whereas PET3m parameters also correlated with DoR ( < 0.05). Harrell C-index values were higher for PET3m measures than for PET1m, though differences were not statistically significant ( > 0.05). On multivariable analysis, older age (HR, 1.10), bridging therapy (HR, 10.91), elevated lactate dehydrogenase (HR, 6.43), increased fibrinogen (HR, 5.27), and higher SUV at PET3m (HR, 11.03) independently predicted poorer OS. There were no significant associations between SUV, MTV, and TLG with CAR T-related toxicities. Semiquantitative PET parameters, such as SUV, MTV, and TLG, at 1 mo and 3 mo after CAR T-cell therapy correlate significantly with OS, PFS, and DoR. [F]FDG PET/CT at 3 mo may offer slightly stronger prognostic discrimination, but both time points can be used for early risk stratification.

摘要

嵌合抗原受体T细胞(CAR T)疗法在治疗复发或难治性大B细胞淋巴瘤方面已显示出显著疗效。然而,近一半的此类患者最终并未实现持久缓解。我们研究了半定量PET参数(即SUV、代谢肿瘤体积[MTV]和总病变糖酵解[TLG])是否能改善CAR T输注后1个月(PET1m)和3个月(PET3m)时的风险分层。在这项前瞻性、单中心队列研究中,大B细胞淋巴瘤患者接受了阿基仑赛或替雷利珠单抗治疗。在基线、输注后1个月和3个月进行[F]FDG PET/CT扫描。MTV和TLG使用SUV阈值4或更高来计算。对患者进行总生存期(OS)、无进展生存期(PFS)和缓解持续时间(DoR)的随访。成像评估基于卢加诺反应评估建议。使用单变量和多变量Cox回归确定预后因素。共纳入61例患者,中位随访时间为18个月。28例(46%)患者死亡。采用对数秩检验的Kaplan-Meier分析表明,Deauville评分(DS)、SUV、MTV和TLG升高与OS显著相关(均P<0.05)。DS临界值任意设定为4。PET1m时SUV、MTV和TLG的最佳临界值分别为9.1、60.8和97.0;而PET3m时分别为6.3、120.1和436.9。PET3m时SUV≥6.3的患者死亡风险增加8倍(风险比[HR]为8.15;95%置信区间为2.81 - 23.6;P<0.01),与低于该临界值的患者相比。同样,PET3m时较高的MTV(≥120.1)产生近10倍的风险(HR为9.87;95%置信区间为3.65 - 26.7;P<0.01)。PET1m和PET3m时的DS、SUV、MTV和TLG均与OS和PFS相关(均P<0.05),而PET3m参数也与DoR相关(P<0.05)。PET3m测量的Harrell C指数值高于PET1m,尽管差异无统计学意义(P>0.05)。多变量分析显示,年龄较大(HR为1.10)、桥接治疗(HR为10.91)、乳酸脱氢酶升高(HR为6.43)、纤维蛋白原增加(HR为5.27)和PET3m时较高的SUV(HR为11.03)独立预测较差的OS。SUV、MTV和TLG与CAR T相关毒性之间无显著关联。CAR T细胞治疗后1个月和3个月的半定量PET参数,如SUV、MTV和TLG,与OS、PFS和DoR显著相关。3个月时的[F]FDG PET/CT可能提供稍强的预后判别能力,但两个时间点均可用于早期风险分层。

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本文引用的文献

[1]
International Benchmark for Total Metabolic Tumor Volume Measurement in Baseline F-FDG PET/CT of Lymphoma Patients: A Milestone Toward Clinical Implementation.

J Nucl Med. 2024-9-3

[2]
Early evaluation of CAR-T cell therapy response in R/R DLBCL patients using F-FDG PET/CT.

Hell J Nucl Med. 2024

[3]
Metabolic PET/CT analysis of aggressive Non-Hodgkin lymphoma prior to Axicabtagene Ciloleucel CAR-T infusion: predictors of progressive disease, survival, and toxicity.

Blood Cancer J. 2023-8-18

[4]
Staging of lymphoma under chimeric antigen receptor T-cell therapy: reasons for discordance among imaging response criteria.

Cancer Imaging. 2023-5-15

[5]
Prognostic value of baseline and early response FDG-PET/CT in patients with refractory and relapsed aggressive B-cell lymphoma undergoing CAR-T cell therapy.

J Cancer Res Clin Oncol. 2023-8

[6]
Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy.

Cancer. 2023-1-15

[7]
Positron emission tomography-imaging assessment for guiding strategy in patients with relapsed/refractory large B-cell lymphoma receiving CAR T cells.

Haematologica. 2023-1-1

[8]
Early FDG-PET response predicts CAR-T failure in large B-cell lymphoma.

Blood Adv. 2022-1-11

[9]
Real World Evidence of CAR T-Cell Therapies for the Treatment of Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma: A Monocentric Experience.

Cancers (Basel). 2021-9-24

[10]
[F]FDG PET-CT in patients with DLBCL treated with CAR-T cell therapy: a practical approach of reporting pre- and post-treatment studies.

Eur J Nucl Med Mol Imaging. 2022-2

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