Omission of Radiotherapy in Primary Mediastinal B-Cell Lymphoma: IELSG37 Trial Results
Authors: Maurizio Martelli, Luca Ceriani, Giovannino Ciccone, Umberto Ricardi, Iryna Kriachok, Barbara Botto, Monica Balzarotti, Alessandra Tucci, Sara Veronica Usai, Vittorio Ruggero Zilioli, Elsa Pennese, Luca Arcaini, Anna Dabrowska-Iwanicka, Andrés J.M. Ferreri, Francesco Merli, Weili Zhao, Luigi Rigacci, Claudia Cellini, David Hodgson, Codruta Ionescu, Carla Minoia, Elisa Lucchini, Michele Spina, Alexander Fosså, Andrea Janikova, Kate Cwynarski, George Mikhaeel, Mats Jerkeman, Alice Di Rocco, Yana Stepanishyna, Umberto Vitolo, Armando Santoro, Alessandro Re, Benedetta Puccini, Jacopo Olivieri, Luigi Petrucci, Sally F. Barrington, Bogdan Malkowski, Ur Metser, Annibale Versari, Stephane Chauvie, Jan Walewski, Marek Trneny, Franco Cavalli, Mary Gospodarowicz, Peter W.M. Johnson, Andrew Davies, Emanuele Zucca, Mary Gospodarowicz, David Hodgson, John Kuruvilla, Li Wang, Weili Zhao, David Balada, Andreas Huettmann, Francesco Angrilli, Ombretta Annibali, Luca Arcaini, Oreste Bagni, Monica Balzarotti, Roberta Battistini, Barbara Botto, Maria Giuseppina Cabras, Teresa Calimeri, Califano Catello, Federica Cavallo, Claudia Cellini, Patrizia Ciammella, Ugo Consoli, Vitaliana De Sanctis, Nicola Di Renzo, Alice Di Rocco, Alberto Fabbri, Angela Ferrari, Andrés J.M. Ferreri, Leonardo Flenghi, Gianluca Gaidano, Guido Gini, Manuel Gotti, Attilio Guarini, Anna Marina Liberati, Elisa Lucchini, Donato Mannina, Maurizio Martelli, Fabio Matrone, Francesco Merli, Carla Minoia, Anna Lia Molinari, Gerardo Musuraca, Luca Nassi, Jacopo Olivieri, Francesco Passamonti, Domenico Pastore, Caterina Patti, Sabrina Pelliccia, Elsa Pennese, Luigi Petrucci, Francesco Piazza, Francesco Pisani, Michele Pizzuti, Samantha Pozzi, Benedetta Puccini, Emanuele Ravano, Alessandro Re, Francesca Re, Luigi Rigacci, Armando Santoro, Marianna Sassone, Michele Spina, Vittorio Stefoni, Caterina Stelitano, Giuseppe Tarantini, Corrado Tarella, Alessandra Tucci, Sara Veronica Usai, Daniele Vallisa, Umberto Vitolo, Francesco Zaja, Manuela Zanni, Vittorio Ruggero Zilioli, Un Merete Fagerli, Alexander Fosså, Anna Dabrowska-Iwanicka, Jan Walewski, Maria Gomes DaSilva, Mats Jerkeman, Ngwa Che Azinwi, Franco Cavalli, Letizia Deantonio, Felicitas Hitz, Codruta Ionescu, Walter Mingrone, Alden Moccia, Urban Novak, Maria Cristina Pirosa, Anastasios Stathis, Emanuele Zucca, Iryna Kriachok, Yana Stepanishyna, Kelly Cozens, Kate Cwynarski, Andrew Davies, Christopher P. Fox, Timothy Illidge, Rod Johnson, Pam McKay, George Mikhaeel, Alison Milne, Shah Nimish, Wendy Osborne, Shankara Paneesha, Andrew Pettitt, Don Ambrose Stevens, Sally F. Barrington, Luca Ceriani Stephane Chauvie Bogdan Malkowski, Ur Metser, Annibale Versari, Luisella Bonomini, Nicoletta Ielmini
Journal: Journal of Clinical Oncology (2024)

PURPOSE The role of consolidation radiotherapy in patients with primary mediastinal B-cell lymphoma (PMBCL) is controversial. METHODS The IELSG37 trial, a randomized noninferiority study, aimed to assess whether irradiation can be omitted in patients with PMBCL with complete metabolic response (CMR) after induction immunochemotherapy. The primary end point was progression-free survival (PFS) at 30 months after random assignment. Patients with CMR were randomly assigned to observation or consolidation radiotherapy (30 Gy). With a noninferiority margin of 10% (assuming a 30-month PFS of 85% in both arms), a sample size of 540 patients was planned with 376 expected to be randomly assigned. RESULTS The observed events were considerably lower than expected; therefore, primary end point analysis was conducted when ≥95% of patients were followed for ≥30 months. Of the 545 patients enrolled, 268 were in CMR after induction and were randomly assigned to observation (n = 132) or radiotherapy (n = 136). The 30-month PFS was 96.2% in the observation arm and 98.5% in the radiotherapy arm, with a stratified hazard ratio of 1.47 (95% CI, 0.34 to 6.28) and absolute risk difference of 0.68% (95% CI, –0.97 to 7.46). The 5-year overall survival (OS) was 99% in both arms. Nonrandomized patients were managed according to local policies. Radiotherapy was the only treatment in 86% of those with Deauville score (DS) 4 and in 57% of those with DS 5. The 5-year PFS and OS of patients with DS 4 (95.8% and 97.5%, respectively) were not significantly different from those of randomly assigned patients. Patients with DS5 had significantly poorer 5-year PFS and OS (60.3% and 74.6%, respectively). CONCLUSION This study, the largest randomized trial of radiotherapy in PMBCL, demonstrated favorable outcomes in patients achieving CMR with no survival impairment for those omitting irradiation.