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

• In Follicular lymphoma patients, 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

Patients with follicular lymphoma (FL) who experience disease progression within 24 months of diagnosis (POD24) have a lower survival. Positron emission tomography (PET) response and circulating tumor DNA (ctDNA) residual disease (MRD) assessment at end of induction therapy (EOI) may allow their early identification. A representative cohort of 141 patients from the RELEVANCE phase III 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 PFS from EOI was not reached (NR) for the 112 patients with undetected ctDNA at EOI versus 17.7 months (95%CI : 1.4-NA) for patients ctDNA MRD (+) (p=0.0038). Similarly, median PFS was NR for the 104 patients with undetected disease on PET at EOI versus 28.3 months (95%CI : 2.9-NR, p=0.0002) for patients with PET(+). Both tests had a negative predictive value (NPV) above 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 for an early prediction of POD24 which may lead to a preemptive treatment decision.