PET interim results could promptly select Follicular Lymphoma patients in need of maintenance therapy. Potential additional value of ctDNA

Background: Follicular Lymphoma (FL) patients frequently achieve long remissions with frontline chemoimmunotherapy (CIT); nevertheless, a subset of patients will experience early progression and a poor outcome. Fluoro-[18F]-deoxy-2-D-glucose positron emission tomography (PET/CT) and liqBio-MRD performed at the end of CIT induction can identify patients at significantly higher risk of relapse. The aim of this study is to analyze if an interim PET/TC scan could earlier identify high-risk FL. Methods: We retrospectively identified 121 patients grade 1–3A FL patients who had end of treatment (EOT) and interim PET/CT (after 4 cycles of frontline CIT) between 2012 and 2022. PET/CT were analyzed using Deauville score (DS). Interim cell free DNA (cfDNA) was available in 15 patients, so we could measure MRD by NGS (Jiménez-Ubieto 2023). Results: Most patients were treated with R-CHOP (n = 94; 78%) or rituximab-bendamustine (n = 24; 20%). Rituximab maintenance (RM) was used in 87%. Median follow-up was 34 months (3–115). A total of 34 patients (28%) relapsed, 21 (17.5%) within 24 months after CIT (POD24). Histological transformation (HT) rate was 2.5%. The EOT CR rate was 81.5%. PET/CTEOT were predictive of relapse, with 2-years PFS 47% in PET/CTEOT(+) vs. 89% in PET/CTEOT(-) (p < .001).On iPET/CT, 41 (34%) patients were PET/CT(+).The estimated 5 year-PFS at was 72% in patients with a negative iPET/CT versus 29% in those with a positive iPET/CT (p < 0.001) (Figure 1a). POD24 was found in 34% and 7.6% of patients with iPET/CT(+) and (-)respectively, (p < 0.001; HR 7.89). iPET/CT(-) presented a negative predictive value of 94% for POD24. Additionally, in 78 patients with iPET/CT(-) and 93 patients with PET/CTEOT(-) MR was not relevant to predict POD24 (2-year PFS of 93.5%/85.7% and 91.3%/87.5%, respectively) (Figure 1b). Notwithstanding, patients with iPET/CT(+) or EOTPET/CT(+) MR had a clear impact in PFS (p < 0.05). Additionally SUVmax >3,7 in the iPET/CT(-) was predictive for HT, regardless of being iPET/CT(-) (6-year TFS of 81.9% vs. 100%). We found trackable mutations in 14 of 15 patients with interim cfDNA MRD analysis (93%). 4/14 patients relapsed after a median of 8.5 months. 3/4 of the relapsing patients had a MRD interim (+) and all the non-relapsing patients a negative MRD test (p < .001). Interestingly, of the 10 non-relapsing patients, 2 have iPET/CT(+) (mesenteric masses). A biopsy excluded lymphoma, confirming the false positive value of the PET/CT. Encore Abstract - previously submitted to EHA 2023 Keywords: Indolent non-Hodgkin lymphoma, Liquid biopsy, PET-CT No conflicts of interests pertinent to the abstract.