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

• Published in: Blood Vol. 146; no. 8; pp. 913 - 925
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.08.2025
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - blood; Circulating Tumor DNA - blood; Circulating Tumor DNA - genetics; Disease Progression; Female; Humans; Lymphoma, Follicular - blood; Lymphoma, Follicular - diagnostic imaging; Lymphoma, Follicular - drug therapy; Lymphoma, Follicular - genetics; Lymphoma, Follicular - mortality; Lymphoma, Follicular - therapy; Male; Middle Aged; Neoplasm, Residual; Positron-Emission Tomography - methods
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2024027727

•In patients with follicular lymphoma, both ctDNA and PET positivity after induction response are associated with shorter PFS.•Only combined ctDNA and PET identify patients at high risk of early relapse (POD24), linked to poor survival. [Display omitted] 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. Patients with the heterogeneous disease follicular lymphoma who experience early progression (within 24 months of diagnosis [POD24]) have outcomes significantly inferior to those of the majority of patients, but prospective identification of POD24 is difficult. In this Plenary Paper, Claudel and colleagues use data from a prospective trial of modern therapies to evaluate the utility of combined end-of-induction measures with positron emission tomography/computed tomography and circulating tumor DNA as a composite biomarker for the prediction of POD24. They found very high specificity and sufficient sensitivity to recommend this combined imaging and genetic marker strategy in future trials that investigate preemptive interventions to circumvent early relapse.