Abstract

Background: Follicular lymphoma (FL) is the second most common NHL. It is generally associated with an indolent course, but a subgroup of patients has worse outcome, lower progression-free-survival (PFS) and higher risk of histological transformation (HT). Since Lugano classification, the Deauville criteria using the 5-point scale (D5PS) is validated as the interpretation method for response assessment PET scans in HL and NHL. Nevertheless, the prognostic value of D5PS in the interim evaluation in FL (PETINT) is not well stablished. Additionally, the quantitative value of SUVmax parameter in the response assessment is almost not studied. Aims: The aim of this study is to evaluate the prognostic value of PETINT evaluation and quantitative mid-induction SUVmax parameter in a cohort of FL patients followed and treated in a single, academic centre with chemo-immunotherapy. Methods: 179 consecutive FL patients were newly diagnosed between 2011 and 2020. 40 patients that did not require systemic treatment and 68 that did not have a PETINT evaluation were excluded. As well, patients with HT (9) and FL grade 3B (4) were excluded. From the 58 remaining patients, clinical, laboratory and PET examinations data was recorded. All patients were Ann-Arbor stage III-IV and were treated with chemo-immunotherapy. PET/CT examinations were acquired at baseline, mid-induction (after 4 cycles of treatment) and end of treatment (EOT). PET positive was considered when Deauville score (DS) was 4 or 5. Statistical analysis was performed with SPSS® using Cox regression, Kaplan-Meier survival curves and log-rank test. Results: The median age at diagnosis was 64 years (26-95) and 29 (50%) patients were female. 33/58 (57%) patients had a high risk FLIPI and 18/55 (33%) had a high risk PRIMA-PI. 37 (64%) patients were treated with R-CHOP and 21 with R-bendamustine. 44 (76%) patients received maintenance with rituximab. After a median follow-up of 43 months, 20 (34%) patients had progression. On PETINT, 19 (32%) patients were PET(+), and 10 of them remained PETEOT(+). Only one patient with PETINT(-), became PETEOT(+). PETINT(+) patients had a median PFS of 31 months compared with a median PFS of 88 months in PETINT(-) (p < 0.001), Figure 1. 38.2% PETINT(+) presented progression of disease in less than 24 months (POD24) vs 5.2% on those who were in PETINT(-), with a p<0.001. PETINT(-) presented a negative predictive value of 95%. No differences in OS was observed. 3/19 (16%) patients with PETINT(+) presented HT vs 1/39 (2%) with PETINT(-). Transformation-free survival was lower in patients with PETINT(+), with a trend towards significance (p= 0.057). Similar PFS results were obtained independently of prognostic index, treatment or maintenance received. Analysing the prognostic value of quantitative SUVmax, patients with SUVmax< 3,8 (28/58; 48%) presented better outcomes, with larger PFS (p < 0.001) and less HT (p= 0.004). Figure 2. Additionally, PET/CT findings at EOT were predictive of relapse, with a median PFS of 30 months in PETEOF (+) vs 88 months in PETEOT(-) (p = 0.005). PETEOT (+) presented a higher risk of HT (p= 0.004). Figure 3. Image:Summary/Conclusion: This study suggests that response assessment by PET at mid-induction is predictive of relapse in advanced stage FL patients treated with 1st line chemo-immunotherapy. With previous conflicting results, further studies are needed to confirm this preliminary data. Probably, new laboratory tests such as MRD monitored by liquid biopsy could improve the detection of this subgroup of high risk patients and help to develop a response-adapted precision therapy.

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