Claudel Alexis, Cottereau Anne-Ségolène, Bachy Emmanuel, Itti Emmanuel, Feugier Pierre, Rossi Cedric, Lemonnier Francois, Camus Vincent, Daguindau Nicolas, Cartron Guillaume, Nicolas-Virelizier Emmanuelle, Mboumba Diana-Laure, Cardoso Christophe, Bommier Côme, Tessoulin Benoit, Fruchart Christophe, Gilbert Adrien, Durot Eric, Fleck Emmanuel, Pica Gian Matteo, Zerazhi Hacene, Guidez Stephanie, Cheminant Morgane, Sarkozy Clementine, Xerri Luc, Vercellino Laetitia, Trabelsi Nesrine, Gomes Lucie, Portugues Cedric, Viailly Pierre-Julien, Delfau-Larue Marie-Hélène, Morschhauser Franck
Department of Immunology Biology, Centre Hospitalier Universitaire Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris-Est, Creteil, Institut Mondor de Recherche Biomedicale, Créteil, France.
Department of Nuclear Medicine, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France.
Blood. 2025 Aug 21;146(8):913-925. doi: 10.1182/blood.2024027727.
Patients with follicular lymphoma who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) minimal residual disease (MRD) assessment at end of induction (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase 3 trial with both available serum samples for ctDNA testing and PET images at randomization and at EOI (week 24) was investigated. Twelve percent were POD24. ctDNA was analyzed using a customized 130-kilobase capture panel, with phased variant (PV) enriched regions representing 39% of the panel. ctDNA was detected in 140 patients (99.3%) at baseline. To optimize specificity, only PVs, found in 124 patients (88%), were considered for ctDNA MRD assessment at EOI. Median progression-free survival (PFS) from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI vs 17.7 months (95% confidence interval [CI], 1.4 to NR) for patients with positive ctDNA (MRD+) (P = .0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI vs 28.3 months (95% CI, 2.9 to NR; P = .0002) for patients with PET positivity. Both tests had a negative predictive value (NPV) of >90% for POD24. The positive predictive value was 58.3% for ctDNA MRD and 45% for PET but increased to 85.7% when both parameters were combined, without alteration of NPV. These data show that the combination of PET response and ctDNA MRD at EOI allows an early prediction of POD24, which may lead to a preemptive treatment decision. This trial was registered at www.clinicaltrials.gov as #NCT01650701.
在诊断后24个月内出现疾病进展（POD24）的滤泡性淋巴瘤患者生存率较低。诱导结束时（EOI）的正电子发射断层扫描（PET）反应和循环肿瘤DNA（ctDNA）微小残留病（MRD）评估可能有助于早期识别这些患者。对来自RELEVANCE 3期试验的141例有代表性的患者进行了研究，这些患者在随机分组时以及EOI（第24周）时均有可用的血清样本用于ctDNA检测和PET图像。12%的患者为POD24。使用定制的130千碱基捕获面板分析ctDNA，其中分阶段变异（PV）富集区域占该面板的39%。基线时在140例患者（99.3%）中检测到ctDNA。为优化特异性，在EOI时仅考虑在124例患者（88%）中发现的PV进行ctDNA MRD评估。EOI时ctDNA未检测到的112例患者的无进展生存期（PFS）中位数未达到（NR），而ctDNA阳性（MRD+）的患者为17.7个月（95%置信区间[CI]，1.4至NR）（P = 0.0038）。同样，EOI时PET未检测到疾病的104例患者的PFS中位数未达到（NR），而PET阳性的患者为28.3个月（95%CI，2.9至NR；P = 0.0002）。两种检测方法对POD24的阴性预测值（NPV）均>90%。ctDNA MRD的阳性预测值为58.3%，PET为45%，但当两个参数结合时增至85.7%，而NPV不变。这些数据表明，EOI时PET反应和ctDNA MRD的结合可早期预测POD24，这可能导致提前做出治疗决策。该试验已在www.clinicaltrials.gov注册，编号为#NCT01650701。
