Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment

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.

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Journal
Blood
Published
2025-06-11
DOI
https://doi.org/10.1182/blood.2024027727
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10
Primary Topic
Lymphoma Diagnosis and Treatment
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article
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article

Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment

Emmanuel Itti, Morgane Cheminant, Laëtitia Vercellino, Alexa Gilbert et al.
10 citations
Blood
Lymphoma Diagnosis and Treatment
14.72
article

Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment

Emmanuel Itti, Morgane Cheminant, Laëtitia Vercellino, Alexa Gilbert, Guillaume Cartron, Nesrine Trabelsi, Cédric Portugues, François Lemonnier, Éric Durot, Clémentine Sarkozy, Luc Xerri, Alexis Claudel, Stéphanie Guidez, Pierre‐Julien Viailly, Franck Morschhauser, Emmanuel Bachy, Gian Matteo Pica, Côme Bommier, Christophe Fruchart, Vincent Camus, Marie‐Hélène Delfau‐Larue, Emmanuel Fleck, Benoît Tessoulin, Anne‐Ségolène Cottereau, Hacène Zerazhi, Cédric Rossi, Nicolas Daguindau, Carlos Cardoso, Pierre Feugier, L Passini Guimarães Gomes, Emmanuelle Nicolas Virelizier, Diana Laure Mbouma
article en
10 citations

Abstract

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.

BloodVol. 146(8)
Université Claude Bernard Lyon 1 (FR), Hôpital Necker-Enfants Malades (FR), Inserm (FR), Université de Bourgogne (FR), Université Paris-Est Créteil (FR), Université Paris Cité (FR), Université de Lille (FR), Centre Hospitalier Universitaire de Lille (FR), Centre Hospitalier Universitaire de Nantes (FR), Centre Hospitalier Universitaire Henri-Mondor (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Montpellier (FR), Assistance Publique – Hôpitaux de Paris (FR), Centre Hospitalier Régional et Universitaire de Nancy (FR), Hospices Civils de Lyon (FR), Centre Hospitalier de Vitré (FR), Centre Léon Bérard (FR), Centre Hospitalier Universitaire de Reims (FR), The Lymphoma Academic Research Organisation (FR), Centre Hospitalier Métropole Savoie (FR), Centre Hospitalier Universitaire de Poitiers (FR), Hôpital Lyon Sud (FR), CHU Dijon Bourgogne (FR), Hôpital Robert-Debré (FR), Hôpitaux Universitaires Henri-Mondor (FR), Centre Hospitalier Annecy Genevois (FR), Laboratoire National Henri Becquerel (FR), Centre Hospitalier de La Rochelle (FR), Hôpital Saint-Louis (FR), Institut Paoli-Calmettes (FR), Centre Virchow-Villermé (FR), Institut Mondor de Recherche Biomédicale (FR), Centre Henri Becquerel, Génomique du cancer et du cerveau, Université Bourgogne Europe (FR), Institut Curie (FR), Université de Reims Champagne-Ardenne (FR), Nantes Université (FR)
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Openalex Percentile: Top 1%
Lymphoma Diagnosis and Treatment
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