Combined PET and ctDNA response as a predictor of POD24 for follicular lymphoma after first-line induction treatment
Alexis Claudel, Anne‐Ségolène Cottereau, Emmanuel Bachy, Emmanuel Itti, Pierre Feugier, Cédric Rossi, François Lemonnier, Vincent Camus, Nicolas Daguindau, Guillaume Cartron, Emmanuelle Nicolas Virelizier, Diana-Laure Mboumba, Christophe Cardoso, Côme Bommier, Benoît Tessoulin, Christophe Fruchart, Alexa Gilbert, Éric Durot, Emmanuel Fleck, Gian Matteo Pica, Hacène Zerazhi, Stéphanie Guidez, Morgane Cheminant, Clémentine Sarkozy, Luc Xerri, Laëtitia Vercellino, Nesrine Trabelsi, L Passini Guimarães Gomes, Cédric Portugues, Pierre‐Julien Viailly, Marie‐Hélène Delfau‐Larue, Franck Morschhauser
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.