Impact of Minimal Residual Disease Analysis in the Era of Rituximab Maintenance in Follicular Lymphoma: Data from “FOLL12” Phase III Trial of the Fondazione Italiana Linfomi

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.339-339
• Main Authors: Ferrero, Simone, Del Giudice, Ilaria, Galimberti, Sara, Gattei, Valter, Marcheselli, Luigi, Genuardi, Elisa, Drandi, Daniela, Pironti, Mariapia, Dogliotti, Irene, Civita, Aurora Maria, Della Starza, Irene, Assanto, Giovanni Manfredi, Guerrini, Francesca, Bono, Clara, Bomben, Riccardo, Boccomini, Carola, Farina, Lucia, Olivieri, Jacopo, Arcaini, Luca, Cavallo, Federica, Ballerini, Filippo, Margiotta Casaluci, Gloria, Zilioli, Vittorio Ruggero, Zanni, Manuela, Musuraca, Gerardo, Merli, Anna, Bianchi, Benedetta, Bolis, Silvia, Pavone, Vincenzo, Chiarenza, Annalisa, Arcari, Annalisa, Califano, Catello, Pozzi, Samantha, Massaia, Massimo, Conconi, Annarita, Perrone, Tommasina, Mannina, Donato, Re, Alessandro, Nizzoli, Maria Elena, Dardanis, Dimitri, Luminari, Stefano, Ladetto, Marco
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-194832

Introduction. Minimal residual disease (MRD) analysis has been largely used in follicular lymphoma (FL) for outcome prediction. However, despite the broad employment of rituximab maintenance for long-term disease control, there are few published data describing the prognostic impact of MRD monitoring during anti-CD20 maintenance or pre-emptive rituximab strategies. Therefore, we performed a wide and comprehensive MRD analysis at several predefined time points in the phase III, “FOLL12” trial [Luminari JCO 2022], sponsored by the Fondazione Italiana Linfomi (FIL). This is the largest MRD-driven clinical trial ever conducted in FL comparing conventional rituximab maintenance (after R-CHOP or BR) vs a combined PET/MRD response-adapted post-induction approach. We here present for the first time the MRD results stratified by post-induction treatment arm. Methods. Peripheral blood(PB) and bone marrow (BM) samples were centralized at the four Italian Euro-MRD certified laboratories of the FIL MRD Network. MRD was assessed with consensus primers on IGH::BCL2 rearrangements by RQ-PCR at end of induction (EOI) and every six months thereafter during either two years rituximab maintenance (reference arm, REF) or a response-adapted approach, offering up to three cycles of four, weekly pre-emptive rituximab infusions only in case of MRD positivity (experimental arm, EXP), till month 24. Results. High MRD negativity rates were obtained at EOI in both treatment arms (REF vs EXP: 92% vs 88% p=0.255), but the MRD kinetics changed overtime during the 24 months after EOI: if 60% of patients steadily maintained MRD negativity, 27% experienced at least one MRD recurrence (being MRD negative at EOI) while 13% converted at least once from MRD positive to MRD negative; importantly, only 1% of patients steadily maintained MRD positivity overtime without clinical relapse. Actually, focusing on the time points after EOI MRD negativity rates decreased in patients of the EXP arm vs patients receiving standard rituximab maintenance, with an overall higher incidence of MRD positivity in EXP vs REF during the 2 years after EOI (relative risk of MRD positivity: 1.78, 95% CI 1.30-2.45, p