End of induction [F]FDG PET is prognostic for progression-free survival and overall survival in follicular lymphoma patients enrolled in the FOLL12 trial.

in European journal of nuclear medicine and molecular imaging by Luca Guerra, Stephane Chauvie, Federico Fallanca, Fabrizio Bergesio, Luigi Marcheselli, Rexhep Durmo, Simona Peano, Antonella Franceschetto, Lavinia Monaco, Emiliano Barbieri, Marco Ladetto, Gerardo Musuraca, Patrizia Tosi, Benedetta Bianchi, Silvia Anna Maria Bolis, Vincenzo Pavone, Annalisa Chiarenza, Annalisa Arcari, Catello Califano, Alessia Bari, Massimo Massaia, Annarita Conconi, Pellegrino Musto, Donato Mannina, Giovanni Roti, Sara Galimberti, Guido Gini, Flavio Falcinelli, Umberto Vitolo, Sara Veronica Usai, Piero Maria Stefani, Adalberto Ibatici, Anna Marina Liberati, Elsa Pennese, Tommasina Perrone, Annibale Versari, Stefano Luminari,

TLDR

  • This study looked at how well a tool called the Deauville score (DS) can predict whether a patient's lymphoma is responding to treatment.
  • The study enrolled patients with a type of lymphoma called follicular lymphoma and randomly assigned them to two different treatment plans.
  • The study found that the DS was a reliable tool to predict whether a patient's lymphoma was responding to treatment, and that the results were consistent across both treatment plans.

Abstract

To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [F]FDG PET (PET) in follicular lymphoma patients. Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97) and 82% (95%CI: 72%-89%) in EOI PET negative (DS1-3) and positive (DS4-5), respectively (HR 4.48; p < 0.001). When DS was associated with FLIPI-2, patients with DS3 or DS1-2 with high FLIPI-2 (3-5) experienced worse OS than patients with DS1-2 and low FLIPI-2 (1-2) (p = 0.003). This study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL. Moreover, although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.

Overview

  • The study evaluates the reliability of the Deauville score (DS) in therapy response assessment and defines the prognostic value of the metabolic response of end of induction (EOI) FDG PET in follicular lymphoma patients.
  • The study enrolled adult patients with untreated grade 1-3a FL/ stage II-IV in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) and randomized them to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm).
  • The primary endpoint was PFS, and the main secondary endpoint was overall survival (OS). The study analyzed 807 follicular lymphoma patients, with 729 (90.4%) baseline and EOI PET available for the analysis.

Comparative Analysis & Findings

  • EOI PET was positive (DS4-5) in 88/729 (12.1%) cases.
  • Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively.
  • The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%).

Implications and Future Directions

  • The study shows that DS is a reliable prognostic tool to evaluate EOI PET in follicular lymphoma patients, with prognostic value maintained both in the standard and experimental arms, making metabolic imaging a robust tool to assess response in FL.
  • Although preliminary, this study provides further information on DS3 patients, who are considered as CMR but show a less favourable PFS than DS1-2 patients.
  • Future research should focus on validating the prognostic value of DS in other lymphoma subtypes and identifying potential biomarkers that could improve the accuracy of the DS.
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