Stefano Luminari1,2, Martina Manni1, Sara Galimberti3, Annibale Versari4, Alessandra Tucci5, Carola Boccomini6, Lucia Farina7, Jacopo Olivieri8, Luigi Marcheselli9, Luca Guerra10,11, Simone Ferrero12, Luca Arcaini13, Federica Cavallo12, Sofya Kovalchuk14, Tetiana Skrypets1,15, Ilaria Del Giudice16, Stephane Chauvie17, Caterina Patti18, Caterina Stelitano19, Francesca Ricci20, Antonello Pinto21, Gloria Margiotta Casaluci22, Vittorio R Zilioli23, Anna Merli24, Marco Ladetto25,26, Silvia Bolis27, Vincenzo Pavone28, Annalisa Chiarenza29, Annalisa Arcari30, Antonella Anastasia5, Alessandra Dondi9, Donato Mannina31, Massimo Federico1. 1. Surgical, Medical and Dental Department of Morphological Sciences Related to Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy. 2. Azienda Unitа Sanitaria Locale-IRCCS, Arcispedale Santa Maria Nuova-Ematologia, Reggio Emilia, Italy. 3. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. 4. Nuclear Medicine Division, Azienda USL IRCCS of Reggio Emilia, Reggio Emilia, Italy. 5. ASST Spedali Civili di Brescia-Ematologia, Brescia, Italy. 6. A.O.U. Città della Salute e della Scienza di Torino-SC Ematologia, Torino, Italy. 7. Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Division of Hematology, Milano, Italy. 8. Azienda Sanitaria Universitaria Friuli Centrale (ASU FC), SOC Clinica Ematologica, Udine, Italy. 9. Fondazione Italiana Linfomi Onlus, Modena, Italy. 10. School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy. 11. Nuclear Medicine, San Gerardo Hospital, ASST Monza, Italy. 12. A.O.U. Città della Salute e della Scienza di Torino, Ematologia Universitaria, Torino, Italy. 13. IRCCS Policlinico S. Matteo di Pavia, Div di Ematologia, Pavia, Italy. 14. Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia, Firenze, Italy. 15. Clinical and Experimental Medicine (CEM), University of Modena and Reggio Emilia, Modena, Italy. 16. Policlinico Umberto I, Università "La Sapienza," Istituto Ematologia, Dipartimento di Medicina Traslazionale e di Precisione, Roma, Italy. 17. Medical Physics Division, Santa Croce e Carle Hospital, Cuneo, Italy. 18. A.O. Ospedali Riuniti Villa Sofia-Cervello, Div di Ematologia, Palermo, Italy. 19. Grande Ospedale Metropolitano Bianchi Melacrino Morelli-Ematologia, Reggio Calabria, Italy. 20. Istituto Clinico Humanitas, U.O. Ematologia, Rozzano, Italy. 21. Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, UOC Ematologia Oncologica, Napoli, Italy. 22. AOU Maggiore della Carità di Novara, SCDU Ematologia, Novara, Italy. 23. ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia, Milano, Italy. 24. Ospedale degli Infermi di Rimini, U.O. di Ematologia, Rimini, Italy. 25. Dipartimento di Medicina Traslazionale Università del Piemonte Orientale, Alessandria, Italy. 26. SC Ematologia, AO SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy. 27. SC di Ematologia, ASST MONZA, Monza, Italy. 28. A.O. C. Panico, U.O.C Ematologia e Trapianto, Tricase, Italy. 29. A.O.O. Policlinico "G. Rodolico-S. Marco," U.O.C. Ematologia, Catania, Italy. 30. Ospedale Guglielmo da Saliceto, U.O.Ematologia, Piacenza, Italy. 31. Azienda Ospedaliera Papardo-UOC di Ematologia, Messina, Italy.
Abstract
PURPOSE: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.
PURPOSE: We compared 2 years of rituximab maintenance (RM) with a response-adapted postinduction approach in patients with follicular lymphoma who responded to induction immunochemotherapy. METHODS: We randomly assigned treatment-naïve, advanced-stage, high-tumor burden follicular lymphoma patients to receive standard RM or a response-adapted postinduction approach on the basis of metabolic response and molecular assessment of minimal residual disease (MRD). The experimental arm used three types of postinduction therapies: for complete metabolic response (CMR) and MRD-negative patients, observation; for CMR and MRD-positive (end of induction or follow-up) patients, four doses of rituximab (one per week, maximum three courses) until MRD-negative; and for non-CMR patients, one dose of ibritumomab tiuxetan followed by standard RM. The study was designed as noninferiority trial with progression-free survival (PFS) as the primary end point. RESULTS: Overall, 807 patients were randomly assigned. After a median follow-up of 53 months (range, 1-92 months), patients in the standard arm had a significantly better PFS than those in the experimental arm (3-year PFS 86% v 72%; P < .001). The better PFS of the standard versus experimental arm was confirmed in all the study subgroups except non-CMR patients (n = 65; P = .274). The 3-year overall survival was 98% (95% CI, 96 to 99) and 97% (95% CI, 95 to 99) in the reference and experimental arms, respectively (P = .238). CONCLUSION: A metabolic and molecular response-adapted therapy as assessed in the FOLL12 study was associated with significantly inferior PFS compared with 2-year RM. The better efficacy of standard RM was confirmed in the subgroup analysis and particularly for patients achieving both CMR and MRD-negative.
Authors: Franck Morschhauser; Loretta Nastoupil; Pierre Feugier; Jean-Marc Schiano de Colella; Hervé Tilly; Maria Lia Palomba; Emmanuel Bachy; Christophe Fruchart; Edward N Libby; Rene-Olivier Casasnovas; Ian W Flinn; Corinne Haioun; Hervé Maisonneuve; Loic Ysebaert; Nancy L Bartlett; Kamal Bouabdallah; Pauline Brice; Vincent Ribrag; Steven Le Gouill; Nicolas Daguindau; Stéphanie Guidez; Gian Matteo Pica; Alejandro Martín García-Sancho; Armondo López-Guillermo; Jean-François Larouche; Kiyoshi Ando; Maria Gomes da Silva; Marc André; Wu Kalung; Laurie H Sehn; Koji Izutsu; Guillaume Cartron; Argyrios Gkasiamis; Russell Crowe; Luc Xerri; Nathan H Fowler; Gilles Salles Journal: J Clin Oncol Date: 2022-08-10 Impact factor: 50.717