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