Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment
Abstract
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.
Article Details
Authors (32)
Alexis Claudel
3U955, Creteil, France
Anne-Ségolène Cottereau
1Hôpital Cochin, APHP, University of Paris Cité, Paris, France
Emmanuel Bachy
Emmanuel Itti
10Department of Nuclear Medicine, Hôpital Henri Mondor, Créteil, France
Pierre Feugier
2Service Hématologie, Centre Hospitalier Régional Universitaire de Nancy–Hôpital Brabois, Université de Lorraine, Nancy, France
Cédric Rossi
19Clinical Hematology, Dijon University Hospital, Dijon, France
François Lemonnier
Princess Margaret Cancer Centre, University Health Network
Vincent Camus
19Centre Henri Becquerel, Rouen, France
Nicolas Daguindau
9Department of Hematology, Centre Hospitalier Annecy Genevois, Metz-Tessy, France
Guillaume Cartron
CHU Montpellier UMR5535, Montpellier, France
Emmanuelle Nicolas-Virelizier
11Department of Hematology, Centre Léon Bérard, Lyon, France
Diana-Laure Mboumba
1Department of Immunology Biology, Centre Hospitalier Universitaire Mondor, Assistance Publique–Hôpitaux de Paris, Université Paris-Est, Creteil, Institut Mondor de Recherche Biomedicale, Créteil, France
Christophe Cardoso
1Department of Immunology Biology, Centre Hospitalier Universitaire Mondor, Assistance Publique–Hôpitaux de Paris, Université Paris-Est, Creteil, Institut Mondor de Recherche Biomedicale, Créteil, France
Côme Bommier
1Santé Department, Université Paris Cité, Paris, France
Benoit Tessoulin
Service d’Hématologie, Centre Hospitalier Universitaire (CHU) Hôtel Dieu, Nantes, France
Christophe Fruchart
45CH Dunkerque, Dunkerque, France
Adrien Gilbert
1Institut Curie, Hematology, Saint Cloud, France
Eric Durot
8CHU Reims, Hematology, Reims, France
Emmanuel Fleck
19CH La Rochelle, La Rochelle, France
Gian Matteo Pica
13CHR Métropole Savoie, Hematology Department, Chambéry, France
Hacene Zerazhi
9centre Hospitalier d'Avignon, Avignon, France
Stephanie Guidez
20Service d'Oncologie Hématologique et Thérapie Cellulaire, Centre Hospitalier Universitaire de Poitiers–Hôpital de la Miletrie, Poitiers, France
Morgane Cheminant
28Service Hématologie Adultes, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France
Clémentine Sarkozy
32Service Hématologie, Institut Curie–Site Saint-Cloud, Saint-Cloud, France
Luc Xerri
40Aix Marseille Université, INSERM, Centre National de la Recherche Scientifique, Institut Paoli-Calmettes, Cancer Research Center of Marseille, Marseille, France
Laetitia Vercellino
23Department of Nuclear Medicine, Hôpital Saint-Louis, Assistance Publique–Hôpitaux de Paris, Paris, France
Nesrine Trabelsi
1Department of Immunology Biology, Centre Hospitalier Universitaire Mondor, Assistance Publique–Hôpitaux de Paris, Université Paris-Est, Creteil, Institut Mondor de Recherche Biomedicale, Créteil, France
Lucie Gomes
24INSERM U918, Centre Henri Becquerel, Rouen, France
Cedric Portugues
7Lyon-Sud Hospital, Department of Biostatistics, LYSARC, Pierre-Bénite, France
Pierre-Julien Viailly
2University of Rouen, Centre Henri Becquerel, INSERM U1245, Rouen, France
Marie-Helene Delfau-Larue
13Department of Immunobiology and Inserm U955, Université Hôpital Henri Mondor, CRETEIL, France
Franck Morschhauser
Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France